Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Oncology
Join Editorial Board Propose a Special Issue
Print ISSN: 1019-6439 Online ISSN: 1791-2423
Journal Cover
June-2017 Volume 50 Issue 6

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2017 Volume 50 Issue 6

Full Size Image

Cover Legend PDF

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Antibody to human α-fetoprotein inhibits cell growth of human hepatocellular carcinoma cells by resuscitating the PTEN molecule: in vitro experiments

  • Authors:
    • Kiyoshi Ohkawa
    • Tadashi Asakura
    • Yutaka Tsukada
    • Tomokazu Matsuura
  • View Affiliations / Copyright

    Affiliations: Stable Isotope Medical Applications Laboratory, Research Center for Medical Science, Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan, Radioisotope Research Facilities, Research Center for Medical Science, Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan, Hachioji Laboratory, SRL Inc., Komiya-cho, Hachioji, Tokyo 192-8535, Japan, Department of Laboratory Medicine, Jikei University School of Medicine, Minato-ku, Tokyo 105-8461, Japan
  • Pages: 2180-2190
    |
    Published online on: May 3, 2017
       https://doi.org/10.3892/ijo.2017.3982
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

It has been proposed that α-fetoprotein (AFP) is a new member of the intracellular signaling molecule family of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway via interaction with the phosphatase and tensin homolog (PTEN). In this study, the effects of anti-human AFP antibody on the functions of PTEN were examined using an AFP-producing human hepatoma cell line. The antibody caused significant inhibition of cell growth, compared to a normal IgG control, with the accumulation of intracellular immune complexes followed by significant reduction of cytosolic functional AFP. Decrease in the amount of AKT phosphorylated on serine (S) 473 indicated that PI3K/AKT signaling was suppressed in the cells. S380-phosphorylated PTEN increased markedly by the second day after antibody treatment, with slight but significant increase in the PTEN protein level. Since phosphorylation at S380 is critical for PTEN stability, the increase in S380-phosphorylated PTEN indicated maintenance of the number of PTEN molecules and the related potential to control PI3K/AKT signaling. p53 protein (P53) significantly, but slightly increased during antibody treatment, because PTEN expression increased the stability and function of P53 via both molecular interactions. P53 phosphorylated at S20 or at S392 dramatically increased, suggesting an increase in the stability, accumulation and activation of P53. Glucose transporter 1 (GLUT1) increased immediately after antibody treatment, pointing to a deficiency of glucose in the cells. Immunofluorescence cytology revealed that antibody-treatment re-distributed GLUT1 molecules throughout the cytoplasm with a reduction of their patchy localization on the cell surface. This suggested that translocation of GLUT1 depends on the PI3K/AKT pathway, in particular on PTEN expression. Antibody therapy targeted at AFP-producing tumor cells showed an inhibitory effect on the PI3K/AKT pathway via the liberation, restoration and functional stabilization of PTEN. PTEN simultaneously induced both P53 activation and intracellular translocation of GLUT1, since these are closely associated with PTEN.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Mizejewski GJ and Allen RP: Immunotherapeutic suppression in transplantable solid tumours. Nature. 250:50–52. 1974. View Article : Google Scholar : PubMed/NCBI

2 

Mizejewski GJ, Young SR and Allen RP: α fetoprotein: Effect of heterologous antiserum on hepatoma cells in vitro. J Natl Cancer Inst. 54:1361–1367. 1975. View Article : Google Scholar : PubMed/NCBI

3 

Mizejewski GJ and Allen RP: α-fetoprotein: Studies of tumor-associated antigen cytotoxicity in mouse hepatoma BW7756. Clin Immunol Immunopathol. 11:307–317. 1978. View Article : Google Scholar : PubMed/NCBI

4 

Mizejewski GJ and Dillon WR: Immunobiologic studies in hepatoma-bearing mice passively immunized to α-fetoprotein. Arch Immunol Ther Exp (Warsz). 27:655–662. 1979.

5 

Tsukada Y, Mikuni M, Watabe H, Nishi S and Hirai H: Effect of anti-alpha-fetoprotein serum on some cultured tumor cells. Int J Cancer. 13:187–195. 1974. View Article : Google Scholar : PubMed/NCBI

6 

Wepsic HT, Tsukada Y, Takeichi N, Nishi S and Hirai H: Effect of horse antibody to rat alpha-fetoprotein upon the growth of AH-66 in Donryu rats. Int J Cancer. 25:655–661. 1980. View Article : Google Scholar : PubMed/NCBI

7 

Koji T, Ishii N, Munehisa T, Kusumoto Y, Nakamura S, Tamenishi A, Hara A, Kobayashi K, Tsukada Y, Nishi S, et al: Localization of radioiodinated antibody to alpha-fetoprotein in hepatoma transplanted in rats and a case report of alpha-fetoprotein antibody treatment of a hepatoma patient. Cancer Res. 40:3013–3015. 1980.PubMed/NCBI

8 

Ohkawa K, Tsukada Y, Hibi N and Hirai H: The inhibitory effects of horse anti-rat AFP antiserum on the uptake of 2-deoxy-D-glucose by AFP-producing rat hepatoma cells. Int J Cancer. 33:497–502. 1984. View Article : Google Scholar : PubMed/NCBI

9 

Tsukada Y, Bischof WK, Hibi N, Hirai H, Hurwitz E and Sela M: Effect of a conjugate of daunomycin and antibodies to rat alpha-fetoprotein on the growth of alpha-fetoprotein-producing tumor cells. Proc Natl Acad Sci USA. 79:621–625. 1982. View Article : Google Scholar : PubMed/NCBI

10 

Tsukada Y, Kato Y, Umemoto N, Takeda Y, Hara T and Hirai H: An anti-alpha-fetoprotein antibody-daunorubicin conjugate with a novel poly-L-glutamic acid derivative as intermediate drug carrier. J Natl Cancer Inst. 73:721–729. 1984.PubMed/NCBI

11 

Tsukada Y, Hurwitz E, Kashi R, Sela M, Hibi N, Hara A and Hirai H: Chemotherapy by intravenous administration of conjugates of daunomycin with monoclonal and conventional anti-rat alpha-fetoprotein antibodies. Proc Natl Acad Sci USA. 79:7896–7899. 1982. View Article : Google Scholar : PubMed/NCBI

12 

Tsukada Y, Hurwitz E, Kashi R, Sela M, Hibi N, Hara A and Hirai H: Effect of a conjugate of daunomycin and purified polyclonal or monoclonal antibodies to rat alpha-fetoprotein on the growth of alpha-fetoprotein-producing tumor cells. Ann NY Acad Sci. 417:262–269. 1983. View Article : Google Scholar : PubMed/NCBI

13 

Kato Y, Tsukada Y, Hara T and Hirai H: Enhanced antitumor activity of mitomycin C conjugated with anti-alpha-fetoprotein antibody by a novel method of conjugation. J Appl Biochem. 5:313–319. 1983.PubMed/NCBI

14 

Tsukada Y, Ohkawa K and Hibi N: Suppression of human alpha-foetoprotein-producing hepatocellular carcinoma growth in nude mice by an anti alpha-foetoprotein antibody-daunorubicin conjugate with a poly-L-glutamic acid derivative as intermediate drug carrier. Br J Cancer. 52:111–116. 1985. View Article : Google Scholar : PubMed/NCBI

15 

Ohkawa K, Hibi N and Tsukada Y: Evaluation of a conjugate of purified antibodies against human AFP-dextran-daunorubicin to human AFP-producing yolk sac tumor cell lines. Cancer Immunol Immunother. 22:81–86. 1986. View Article : Google Scholar : PubMed/NCBI

16 

Tsukada Y, Ohkawa K and Hibi N: Therapeutic effect of treatment with polyclonal or monoclonal antibodies to alpha-fetoprotein that have been conjugated to daunomycin via a dextran bridge: Studies with an alpha-fetoprotein-producing rat hepatoma tumor model. Cancer Res. 47:4293–4295. 1987.PubMed/NCBI

17 

Ohkawa K, Tsukada Y, Hibi N, Umemoto N and Hara T: Selective in vitro and in vivo growth inhibition against human yolk sac tumor cell lines by purified antibody against human alpha-fetoprotein conjugated with mitomycin C via human serum albumin. Cancer Immunol Immunother. 23:81–86. 1986. View Article : Google Scholar : PubMed/NCBI

18 

Kim EE, DeLand FH, Nelson MO, Bennett S, Simmons G, Alpert E and Goldenberg DM: Radioimmunodetection of cancer with radiolabeled antibodies to alpha-fetoprotein. Cancer Res. 40:3008–3012. 1980.PubMed/NCBI

19 

Kim EE, Deland FH, Casper S, Corgan RL, Primus FJ and Goldenberg DM: Radioimmunodetection of colorectal cancer. Cancer. 45(Suppl): 1243–1247. 1980. View Article : Google Scholar : PubMed/NCBI

20 

Uriel J, Villacampa MJ, Moro R, Naval J and Failly-Crépin C: Uptake of radiolabeled a-fetoprotein by mouse mammary carcinomas and its usefulness in tumor scintigraphy. Cancer Res. 44:5314–5319. 1984.PubMed/NCBI

21 

Goldenberg DM: Cancer imaging with CEA antibodies: Historical and current perspectives. Int J Biol Markers. 7:183–188. 1992.PubMed/NCBI

22 

Behr TM, Liersch T, Greiner-Bechert L, Griesinger F, Béhé M, Markus PM, Gratz S, Angerstein C, Brittinger G, Becker H, et al: Radioimmunotherapy of small-volume disease of metastatic colorectal cancer. Cancer. 94(Suppl): 1373–1381. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Aarts F, Boerman OC, Sharkey RM, Hendriks T, Chang CH, McBride WJ, Bleichrodt RP, Oyen WJ and Goldenberg DM: Pretargeted radioimmunoscintigraphy in patients with primary colorectal cancer using a bispecific anticarcinoembryonic antigen CEA X anti-di-diethylenetriaminepentaacetic acid F(ab′)2 antibody. Cancer. 116(Suppl): 1111–1117. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Mizejewski GJ: Biological role of alpha-fetoprotein in cancer: Prospects for anticancer therapy. Expert Rev Anticancer Ther. 2:709–735. 2002. View Article : Google Scholar : PubMed/NCBI

25 

Li MS, Li PF, Yang FY, He SP, Du GG and Li G: The intracellular mechanism of alpha-fetoprotein promoting the proliferation of NIH 3T3 cells. Cell Res. 12:151–156. 2002. View Article : Google Scholar : PubMed/NCBI

26 

Li MS, Li PF, He SP, Du GG and Li G: The promoting molecular mechanism of alpha-fetoprotein on the growth of human hepatoma Bel7402 cell line. World J Gastroenterol. 8:469–475. 2002. View Article : Google Scholar : PubMed/NCBI

27 

Li P, Wang SS, Liu H, Li N, McNutt MA, Li G and Ding HG: Elevated serum alpha fetoprotein levels promote pathological progression of hepatocellular carcinoma. World J Gastroenterol. 17:4563–4571. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Moro R, Gulyaeva-Tcherkassova J and Stieber P: Increased alpha-fetoprotein receptor in the serum of patients with early-stage breast cancer. Curr Oncol. 19:e1–e8. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Wang S, Jiang W, Chen X, Zhang C, Li H, Hou W, Liu Z, McNutt MA, Lu F and Li G: Alpha-fetoprotein acts as a novel signal molecule and mediates transcription of Fn14 in human hepatocellular carcinoma. J Hepatol. 57:322–329. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Zhu M, Lin B, Zhou P and Li M: Molecular analysis of AFP and HSA interactions with PTEN potein. BioMed Res Int. 2015:2569162015. View Article : Google Scholar

31 

Mizejewski GJ: Nonsecreted cytoplasmic alpha-fetoprotein: A newly discovered role in intracellular signaling and regulation. An update and commentary. Tumour Biol. 36:9857–9864. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Li M, Li H, Li C, Wang S, Jiang W, Liu Z, Zhou S, Liu X, McNutt MA and Li G: Alpha-fetoprotein: A new member of intracellular signal molecules in regulation of the PI3K/AKT signaling in human hepatoma cell lines. Int J Cancer. 128:524–532. 2011. View Article : Google Scholar

33 

Gao R, Cai C, Gan J, Yang X, Shuang Z, Liu M, Li S and Tang H: miR-1236 down-regulates alpha-fetoprotein, thus causing PTEN accumulation, which inhibits the PI3K/Akt pathway and malignant phenotype in hepatoma cells. Oncotarget. 6:6014–6028. 2015. View Article : Google Scholar : PubMed/NCBI

34 

Zhu M, Guo J, Li W, Lu Y, Fu S, Xie X, Xia H, Dong X, Chen Y, Quan M, et al: Hepatitis B virus X protein induces expression of alpha-fetoprotein and activates PI3K/mTOR signaling pathway in liver cells. Oncotarget. 6:12196–12208. 2015. View Article : Google Scholar : PubMed/NCBI

35 

Su R, Nan H, Guo H, Ruan Z, Jiang L, Song Y and Nan K: Associations of components of PTEN/AKT/mTOR pathway with cancer stem cell markers and prognostic value of these biomarkers in hepatocellular carcinoma. Hepatol Res. 46:1380–1391. 2016. View Article : Google Scholar : PubMed/NCBI

36 

Zhu M, Guo J, Xia H, Li W, Lu Y, Dong X, Chen Y, Xie X, Fu S and Li M: Alpha-fetoprotein activates AKT/mTOR signaling to promote CXCR4 expression and migration of hepatoma cells. Oncoscience. 2:59–70. 2015. View Article : Google Scholar : PubMed/NCBI

37 

Ji X, Shen Y, Sun H and Gao X: A novel anti-alpha-fetoprotein single-chain variable fragment displays anti-tumor effects in HepG2 cells as a single agent or in combination with paclitaxel. Tumour Biol. 37:10085–10096. 2016. View Article : Google Scholar : PubMed/NCBI

38 

Matsumoto M, Matsuura T, Aoki K, Maehashi H, Iwamoto T, Ohkawa K, Yoshida K, Yanaga K and Takada K: An efficient system for secretory production of fibrinogen using a hepatocellular carcinoma cell line. Hepatol Res. 45:315–325. 2015. View Article : Google Scholar

39 

Nakabayashi H, Taketa K, Miyano K, Yamane T and Sato J: Growth of human hepatoma cells lines with differentiated functions in chemically defined medium. Cancer Res. 42:3858–3863. 1982.PubMed/NCBI

40 

Ohkawa K, Tsukada Y, Murae M, Kimura E, Takada K, Abe T, Terashima Y and Mitani K: Serum levels and biochemical characteristics of human ovarian carcinoma-associated antigen defined by murine monoclonal antibody, CF511. Br J Cancer. 60:953–960. 1989. View Article : Google Scholar : PubMed/NCBI

41 

Baumann H and Doyle D: Metabolic fate of cell surface glycoproteins during immunoglobulin-induced internalization. Cell. 21:897–907. 1980. View Article : Google Scholar : PubMed/NCBI

42 

Press OW, Hansen JA, Farr A and Martin PJ: Endocytosis and degradation of murine anti-human CD3 monoclonal antibodies by normal and malignant T-lymphocytes. Cancer Res. 48:2249–2257. 1988.PubMed/NCBI

43 

Kyriakos RJ, Shih LB, Ong GL, Patel K, Goldenberg DM and Mattes MJ: The fate of antibodies bound to the surface of tumor cells in vitro. Cancer Res. 52:835–842. 1992.PubMed/NCBI

44 

McEwan WA, Tam JC, Watkinson RE, Bidgood SR, Mallery DL and James LC: Intracellular antibody-bound pathogens stimulate immune signaling via the Fc receptor TRIM21. Nat Immunol. 14:327–336. 2013. View Article : Google Scholar : PubMed/NCBI

45 

Watkinson RE, McEwan WA and James LC: Intracellular antibody immunity. J Clin Immunol. 34(Suppl 1): S30–S34. 2014. View Article : Google Scholar : PubMed/NCBI

46 

Yoshikawa M, Mukai Y, Okada Y, Tsumori Y, Tsunoda S, Tsutsumi Y, Aird WC, Yoshioka Y, Okada N, Doi T, et al: Robo4 is an effective tumor endothelial marker for antibody-drug conjugates based on the rapid isolation of the anti-Robo4 cell-internalizing antibody. Blood. 121:2804–2813. 2013. View Article : Google Scholar : PubMed/NCBI

47 

Ha KD, Bidlingmaier SM, Su Y, Lee NK and Liu B: Identification of novel macropinocytosing human antibodies by phage display and high-content analysis. Methods Enzymol. 585:91–110. 2017. View Article : Google Scholar : PubMed/NCBI

48 

Miura K, Law SW, Nishi S and Tamaoki T: Isolation of alphafetoprotein messenger RNA from mouse yolk sac. J Biol Chem. 254:5515–5521. 1979.PubMed/NCBI

49 

Zhou BP, Liao Y, Xia W, Spohn B, Lee MH and Hung MC: Cytoplasmic localization of p21Cip1/WAF1 by Akt-induced phosphorylation in HER-2/neu-overexpressing cells. Nat Cell Biol. 3:245–252. 2001. View Article : Google Scholar : PubMed/NCBI

50 

Chung JH and Eng C: Nuclear-cytoplasmic partitioning of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) differentially regulates the cell cycle and apoptosis. Cancer Res. 65:8096–8100. 2005. View Article : Google Scholar : PubMed/NCBI

51 

Chung JH, Ginn-Pease ME and Eng C: Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has nuclear localization signal-like sequences for nuclear import mediated by major vault protein. Cancer Res. 65:4108–4116. 2005. View Article : Google Scholar : PubMed/NCBI

52 

Chung JH, Ostrowski MC, Romigh T, Minaguchi T, Waite KA and Eng C: The ERK1/2 pathway modulates nuclear PTEN-mediated cell cycle arrest by cyclin D1 transcriptional regulation. Hum Mol Genet. 15:2553–2559. 2006. View Article : Google Scholar : PubMed/NCBI

53 

Gil A, Andrés-Pons A, Fernández E, Valiente M, Torres J, Cervera J and Pulido R: Nuclear localization of PTEN by a Ran-dependent mechanism enhances apoptosis: Involvement of an N-terminal nuclear localization domain and multiple nuclear exclusion motifs. Mol Biol Cell. 17:4002–4013. 2006. View Article : Google Scholar : PubMed/NCBI

54 

Al-Khouri AM, Ma Y, Togo SH, Williams S and Mustelin T: Cooperative phosphorylation of the tumor suppressor phosphatase and tensin homologue (PTEN) by casein kinases and glycogen synthase kinase 3beta. J Biol Chem. 280:35195–35202. 2005. View Article : Google Scholar : PubMed/NCBI

55 

Tamguney T and Stokoe D: New insights into PTEN. J Cell Sci. 120:4071–4079. 2007. View Article : Google Scholar : PubMed/NCBI

56 

Georgescu MM, Kirsch KH, Akagi T, Shishido T and Hanafusa H: The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region. Proc Natl Acad Sci USA. 96:10182–10187. 1999. View Article : Google Scholar : PubMed/NCBI

57 

Tolkacheva T and Chan AM: Inhibition of H-Ras transformation by the PTEN/MMAC1/TEP1 tumor suppressor gene. Oncogene. 19:680–689. 2000. View Article : Google Scholar : PubMed/NCBI

58 

Maccario H, Perera NM, Davidson L, Downes CP and Leslie NR: PTEN is destabilized by phosphorylation on Thr366. Biochem J. 405:439–444. 2007. View Article : Google Scholar : PubMed/NCBI

59 

Torres J and Pulido R: The tumor suppressor PTEN is phosphorylated by the protein kinase CK2 at its C terminus. Implications for PTEN stability to proteasome-mediated degradation. J Biol Chem. 276:993–998. 2001. View Article : Google Scholar

60 

Milella M, Falcone I, Conciatori F, Cesta Incani U, Del Curatolo A, Inzerilli N, Nuzzo CM, Vaccaro V, Vari S, Cognetti F, et al: PTEN: Multiple functions in human malignant tumors. Front Oncol. 5:242015. View Article : Google Scholar : PubMed/NCBI

61 

Vazquez F, Ramaswamy S, Nakamura N and Sellers WR: Phosphorylation of the PTEN tail regulates protein stability and function. Mol Cell Biol. 20:5010–5018. 2000. View Article : Google Scholar : PubMed/NCBI

62 

Birle D, Bottini N, Williams S, Huynh H, deBelle I, Adamson E and Mustelin T: Negative feedback regulation of the tumor suppressor PTEN by phosphoinositide-induced serine phosphorylation. J Immunol. 169:286–291. 2002. View Article : Google Scholar : PubMed/NCBI

63 

Okahara F, Ikawa H, Kanaho Y and Maehama T: Regulation of PTEN phosphorylation and stability by a tumor suppressor candidate protein. J Biol Chem. 279:45300–45303. 2004. View Article : Google Scholar : PubMed/NCBI

64 

Okahara F, Itoh K, Nakagawara A, Murakami M, Kanaho Y and Maehama T: Critical role of PICT-1, a tumor suppressor candidate, in phosphatidylinositol 3,4,5-trisphosphate signals and tumorigenic transformation. Mol Biol Cell. 17:4888–4895. 2006. View Article : Google Scholar : PubMed/NCBI

65 

Doble BW and Woodgett JR: GSK-3: Tricks of the trade for a multi-tasking kinase. J Cell Sci. 116:1175–1186. 2003. View Article : Google Scholar : PubMed/NCBI

66 

Saini MK and Sanyal SN: PTEN regulates apoptotic cell death through PI3-K/Akt/GSK3p signaling pathway in DMH induced early colon carcinogenesis in rat. Exp Mol Pathol. 93:135–146. 2012. View Article : Google Scholar : PubMed/NCBI

67 

Tibarewal P, Zilidis G, Spinelli L, Schurch N, Maccario H, Gray A, Perera NM, Davidson L, Barton GJ and Leslie NR: PTEN protein phosphatase activity correlates with control of gene expression and invasion, a tumor-suppressing phenotype, but not with AKT activity. Sci Signal. 5:ra182012. View Article : Google Scholar : PubMed/NCBI

68 

Freeman DJ, Li AG, Wei G, Li HH, Kertesz N, Lesche R, Whale AD, Martinez-Diaz H, Rozengurt N, Cardiff RD, et al: PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms. Cancer Cell. 3:117–130. 2003. View Article : Google Scholar : PubMed/NCBI

69 

Li AG, Piluso LG, Cai X, Wei G, Sellers WR and Liu X: Mechanistic insights into maintenance of high p53 acetylation by PTEN. Mol Cell. 23:575–587. 2006. View Article : Google Scholar : PubMed/NCBI

70 

Hupp TR, Meek DW, Midgley CA and Lane DP: Regulation of the specific DNA binding function of p53. Cell. 71:875–886. 1992. View Article : Google Scholar : PubMed/NCBI

71 

Sakaguchi K, Sakamoto H, Lewis MS, Anderson CW, Erickson JW, Appella E and Xie D: Phosphorylation of serine 392 stabilizes the tetramer formation of tumor suppressor protein p53. Biochemistry. 36:10117–10124. 1997. View Article : Google Scholar : PubMed/NCBI

72 

Shieh SY, Taya Y and Prives C: DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel site, Ser20, requires tetramerization. EMBO J. 18:1815–1823. 1999. View Article : Google Scholar : PubMed/NCBI

73 

Oda K, Arakawa H, Tanaka T, Matsuda K, Tanikawa C, Mori T, Nishimori H, Tamai K, Tokino T, Nakamura Y, et al: p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell. 102:849–862. 2000. View Article : Google Scholar : PubMed/NCBI

74 

Hirao A, Kong YY, Matsuoka S, Wakeham A, Ruland J, Yoshida H, Liu D, Elledge SJ and Mak TW: DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science. 287:1824–1827. 2000. View Article : Google Scholar : PubMed/NCBI

75 

Haupt Y, Maya R, Kazaz A and Oren M: Mdm2 promotes the rapid degradation of p53. Nature. 387:296–299. 1997. View Article : Google Scholar : PubMed/NCBI

76 

Mayo LD and Donner DB: A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc Natl Acad Sci USA. 98:11598–11603. 2001. View Article : Google Scholar : PubMed/NCBI

77 

Zhou BP, Liao Y, Xia W, Zou Y, Spohn B and Hung MC: HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nat Cell Biol. 3:973–982. 2001. View Article : Google Scholar : PubMed/NCBI

78 

Morani F, Phadngam S, Follo C, Titone R, Aimaretti G, Galetto A, Alabiso O and Isidoro C: PTEN regulates plasma membrane expression of glucose transporter 1 and glucose uptake in thyroid cancer cells. J Mol Endocrinol. 53:247–258. 2014. View Article : Google Scholar : PubMed/NCBI

79 

Samih N, Hovsepian S, Aouani A, Lombardo D and Fayet G: Glut-1 translocation in FRTL-5 thyroid cells: Role of phosphatidylinositol 3-kinase and N-glycosylation. Endocrinology. 141:4146–4155. 2000. View Article : Google Scholar : PubMed/NCBI

80 

Hajduch E, Litherland GJ and Hundal HS: Protein kinase B (PKB/Akt) - a key regulator of glucose transport? FEBS Lett. 492:199–203. 2001. View Article : Google Scholar : PubMed/NCBI

81 

Ciampi R, Vivaldi A, Romei C, Del Guerra A, Salvadori P, Cosci B, Pinchera A and Elisei R: Expression analysis of facilitative glucose transporters (GLUTs) in human thyroid carcinoma cell lines and primary tumors. Mol Cell Endocrinol. 291:57–62. 2008. View Article : Google Scholar : PubMed/NCBI

82 

Wang CH, Wey KC, Mo LR, Chang KK, Lin RC and Kuo JJ: Current trends and recent advances in diagnosis, therapy, and prevention of hepatocellular carcinoma. Asian Pac J Cancer Prev. 16:3595–3604. 2015. View Article : Google Scholar : PubMed/NCBI

83 

Taketomi A: Clinical trials of antiangiogenic therapy for hepatocellular carcinoma. Int J Clin Oncol. 21:213–218. 2016. View Article : Google Scholar : PubMed/NCBI

84 

Dhir M, Melin AA, Douaiher J, Lin C, Zhen WK, Hussain SM, Geschwind JF, Doyle MB, Abou-Alfa GK and Are C: A review and update of treatment options and controversies in the management of hepatocellular carcinoma. Ann Surg. 263:1112–1125. 2016. View Article : Google Scholar : PubMed/NCBI

85 

Lin J, Wu L, Bai X, Xie Y, Wang A, Zhang H, Yang X, Wan X, Lu X, Sang X, et al: Combination treatment including targeted therapy for advanced hepatocellular carcinoma. Oncotarget. 7:71036–71051. 2016.PubMed/NCBI

86 

Nakata K, Muro T, Furukawa R, Kono K, Kusumoto Y, Ishii N, Munehisa T, Koji T and Nagataki S: Presence of immunoglobulin G in human sera binding to alphafetoprotein. Oncodev Biol Med. 4:C101–C104. 1983.PubMed/NCBI

87 

Asano T, Yamada N, Ochiai T, Sato H and Fukao T: Presence of anti-AFP-antibody producing B cells in peripheral blood lymphocyte of hepatocellular carcinoma patient. Nihon Shokakibyo Gakkai Zasshi. 81:2781984.In Japanese.

88 

Sassi F, Ayed K, el Gaied A and Dellagi K: Presence of antialphafetoprotein immunoglobulin G in serum of a patient with hepatocellular carcinoma. Gastroenterol Clin Biol. 15:661–662. 1991.in French.

89 

Liu H, Zhang J, Wang S, Pang Z, Wang Z, Zhou W and Wu M: Screening of autoantibodies as potential biomarkers for hepatocellular carcinoma by using T7 phase display system. Cancer Epidemiol. 36:82–88. 2012. View Article : Google Scholar

90 

Negm OH, Hamed MR, Schoen RE, Whelan RL, Steele RJ, Scholefield J, Dilnot EM, Shantha Kumara HM, Robertson JF and Sewell HF: Human blood autoantibodies in the detection of colorectal cancer. PLoS One. 11:e01569712016. View Article : Google Scholar : PubMed/NCBI

91 

Ura Y, Ochi Y, Hamazu M, Ishida M, Nakajima K and Watanabe T: Studies on circulating antibody against carcinoembryonic antigen (CEA) and CEA-like antigen in cancer patients. Cancer Lett. 25:283–295. 1985. View Article : Google Scholar : PubMed/NCBI

92 

Konstadoulakis MM, Syrigos KN, Albanopoulos C, Mayers G and Golematis B: The presence of anti-carcinoembryonic antigen (CEA) antibodies in the sera of patients with gastrointestinal malignancies. J Clin Immunol. 14:310–313. 1994. View Article : Google Scholar : PubMed/NCBI

93 

Haidopoulos D, Konstadoulakis MM, Antonakis PT, Alexiou DG, Manouras AM, Katsaragakis SM and Androulakis GF: Circulating anti-CEA antibodies in the sera of patients with breast cancer. Eur J Surg Oncol. 26:742–746. 2000. View Article : Google Scholar : PubMed/NCBI

94 

Ladd J, Lu H, Taylor AD, Goodell V, Disis ML and Jiang S: Direct detection of carcinoembryonic antigen autoantibodies in clinical human serum samples using a surface plasmon resonance sensor. Colloids Surf B Biointerfaces. 70:1–6. 2009. View Article : Google Scholar : PubMed/NCBI

95 

Zhu M, Li W, Lu Y, Dong X, Lin B, Chen Y, Zhang X, Guo J and Li M: HBx drives alpha fetoprotein expression to promote initiation of liver cancer stem cells through activating PI3K/AKT signal pathway. Int J Cancer. 140:1346–1355. 2017. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ohkawa K, Asakura T, Tsukada Y and Matsuura T: Antibody to human α-fetoprotein inhibits cell growth of human hepatocellular carcinoma cells by resuscitating the PTEN molecule: in vitro experiments. Int J Oncol 50: 2180-2190, 2017.
APA
Ohkawa, K., Asakura, T., Tsukada, Y., & Matsuura, T. (2017). Antibody to human α-fetoprotein inhibits cell growth of human hepatocellular carcinoma cells by resuscitating the PTEN molecule: in vitro experiments. International Journal of Oncology, 50, 2180-2190. https://doi.org/10.3892/ijo.2017.3982
MLA
Ohkawa, K., Asakura, T., Tsukada, Y., Matsuura, T."Antibody to human α-fetoprotein inhibits cell growth of human hepatocellular carcinoma cells by resuscitating the PTEN molecule: in vitro experiments". International Journal of Oncology 50.6 (2017): 2180-2190.
Chicago
Ohkawa, K., Asakura, T., Tsukada, Y., Matsuura, T."Antibody to human α-fetoprotein inhibits cell growth of human hepatocellular carcinoma cells by resuscitating the PTEN molecule: in vitro experiments". International Journal of Oncology 50, no. 6 (2017): 2180-2190. https://doi.org/10.3892/ijo.2017.3982
Copy and paste a formatted citation
x
Spandidos Publications style
Ohkawa K, Asakura T, Tsukada Y and Matsuura T: Antibody to human α-fetoprotein inhibits cell growth of human hepatocellular carcinoma cells by resuscitating the PTEN molecule: in vitro experiments. Int J Oncol 50: 2180-2190, 2017.
APA
Ohkawa, K., Asakura, T., Tsukada, Y., & Matsuura, T. (2017). Antibody to human α-fetoprotein inhibits cell growth of human hepatocellular carcinoma cells by resuscitating the PTEN molecule: in vitro experiments. International Journal of Oncology, 50, 2180-2190. https://doi.org/10.3892/ijo.2017.3982
MLA
Ohkawa, K., Asakura, T., Tsukada, Y., Matsuura, T."Antibody to human α-fetoprotein inhibits cell growth of human hepatocellular carcinoma cells by resuscitating the PTEN molecule: in vitro experiments". International Journal of Oncology 50.6 (2017): 2180-2190.
Chicago
Ohkawa, K., Asakura, T., Tsukada, Y., Matsuura, T."Antibody to human α-fetoprotein inhibits cell growth of human hepatocellular carcinoma cells by resuscitating the PTEN molecule: in vitro experiments". International Journal of Oncology 50, no. 6 (2017): 2180-2190. https://doi.org/10.3892/ijo.2017.3982
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team