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
September-2015 Volume 47 Issue 3

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
September-2015 Volume 47 Issue 3

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

GD2 ganglioside specific antibody treatment downregulates PI3K/Akt/mTOR signaling network in human neuroblastoma cell lines

  • Authors:
    • Małgorzata Durbas
    • Irena Horwacik
    • Elżbieta Boratyn
    • Elżbieta Kamycka
    • Hanna Rokita
  • View Affiliations / Copyright

    Affiliations: Laboratory of Molecular Genetics and Virology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Kraków, Poland
  • Pages: 1143-1159
    |
    Published online on: July 2, 2015
       https://doi.org/10.3892/ijo.2015.3070
  • 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

Mechanisms leading to inhibitory effects of an anti-GD2 ganglioside (GD2) 14G2a mouse monoclonal antibody (mAb) and PI3K/Akt/mTOR pathway inhibitors on human neuroblastoma cell survival were studied in vitro. We have recently shown on IMR-32, CHP‑134, and LA-N-1 neuroblastoma cells that targeting GD2 with the mAb decreases cell viability of the cell lines. In this study we used cytotoxicity assays, proteomic arrays and immunoblotting to evaluate the response of the three cell lines to the anti‑GD2 14G2a mAb and specific PI3K/Akt/mTOR pathway inhibitors. We show here that the mAb modulates intracellular signal transduction through changes in several kinases and their substrates phosphorylation. More detailed analysis of the PI3K/Akt/mTOR pathway showed significant decrease in activity of Akt, mTOR, p70 S6 and 4E-BP1 proteins and transient increase in PTEN (a suppressor of the pathway), leading to inhibition of the signaling network responsible for stimulation of translation and proliferation. Additionally, combining the GD2-specific 14G2a mAb with an Akt inhibitor (perifosine), dual mTOR/PI3K inhibitors (BEZ-235 and SAR245409), and a pan-PI3K inhibitor (LY294002) was shown to enhance cytotoxic effects against IMR-32, CHP‑134 and LA-N-1 cells. Our study extends knowledge on mechanisms of action of the 14G2a mAb on the neuroblastoma cells. Also, it stresses the need for further delineation of molecular signal orchestration aimed at more reasonable selection of drugs to target key cellular pathways in quest for better cure for neuroblastoma patients.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

View References

1 

Modak S and Cheung N-K: Neuroblastoma: Therapeutic strategies for a clinical enigma. Cancer Treat Rev. 36:307–317. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Iżycka-Świeszewska E, Drożyńska E, Rzepko R, Kobierska-Gulida G, Grajkowska W, Perek D and Balcerska A: Analysis of PI3K/AKT/mTOR signalling pathway in high risk neuroblastic tumours. Pol J Pathol. 61:192–198. 2010.

3 

Cheung N-KV and Dyer MA: Neuroblastoma: Developmental biology, cancer genomics and immunotherapy. Nat Rev Cancer. 13:397–411. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Hara J: Development of treatment strategies for advanced neuroblastoma. Int J Clin Oncol. 17:196–203. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, Smith M, Anderson B, Villablanca JG, Matthay KK, et al; Children's Oncology Group. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N Engl J Med. 363:1324–1334. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Aixinjueluo W and Furukawa K, Zhang Q, Hamamura K, Tokuda N, Yoshida S, Ueda R and Furukawa K: Mechanisms for the apoptosis of small cell lung cancer cells induced by anti-GD2 monoclonal antibodies: Roles of anoikis. J Biol Chem. 280:29828–29836. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Yoshida S, Kawaguchi H, Sato S, Ueda R and Furukawa K: An anti-GD2 monoclonal antibody enhances apoptotic effects of anti-cancer drugs against small cell lung cancer cells via JNK (c-Jun terminal kinase) activation. Jpn J Cancer Res. 93:816–824. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Kowalczyk A, Gil M, Horwacik I, Odrowąż Z, Kozbor D and Rokita H: The GD2-specific 14G2a monoclonal antibody induces apoptosis and enhances cytotoxicity of chemotherapeutic drugs in IMR-32 human neuroblastoma cells. Cancer Lett. 281:171–182. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Horwacik I, Durbas M, Boratyn E, Węgrzyn P and Rokita H: Targeting GD2 ganglioside and Aurora A kinase as a dual strategy leading to cell death in cultures of human neuroblastoma cells. Cancer Lett. 341:248–264. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Cochonneau D, Terme M, Michaud A, Dorvillius M, Gautier N, Frikeche J, Alvarez-Rueda N, Bougras G, Aubry J, Paris F, et al: Cell cycle arrest and apoptosis induced by O-acetyl-GD2-specific monoclonal antibody 8B6 inhibits tumor growth in vitro and in vivo. Cancer Lett. 333:194–204. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Samuels Y and Ericson K: Oncogenic PI3K and its role in cancer. Curr Opin Oncol. 18:77–82. 2006. View Article : Google Scholar

12 

Fruman DA and Rommel C: PI3K and cancer: Lessons, challenges and opportunities. Nat Rev Drug Discov. 13:140–156. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Zhang L, Zhou F and ten Dijke P: Signaling interplay between transforming growth factor-β receptor and PI3K/AKT pathways in cancer. Trends Biochem Sci. 38:612–620. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Hers I, Vincent EE and Tavaré JM: Akt signalling in health and disease. Cell Signal. 23:1515–1527. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Laplante M and Sabatini DM: mTOR signaling in growth control and disease. Cell. 149:274–293. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Rodon J, Dienstmann R, Serra V and Tabernero J: Development of PI3K inhibitors: Lessons learned from early clinical trials. Nat Rev Clin Oncol. 10:143–153. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Dienstmann R, Rodon J, Serra V and Tabernero J: Picking the point of inhibition: A comparative review of PI3K/AKT/mTOR pathway inhibitors. Mol Cancer Ther. 13:1021–1031. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Suzuki YJ, Mizuno M and Packer L: Signal transduction for nuclear factor-kappa B activation. Proposed location of antioxidant-inhibitable step. J Immunol. 153:5008–5015. 1994.PubMed/NCBI

19 

Niehrs C: The complex world of WNT receptor signalling. Nat Rev Mol Cell Biol. 13:767–779. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Koul HK, Pal M and Koul S: Role of p38 MAP kinase signal transduction in solid tumors. Genes Cancer. 4:342–359. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Liu Y, Gorospe M, Yang C and Holbrook NJ: Role of mitogen-activated protein kinase phosphatase during the cellular response to genotoxic stress. Inhibition of c-Jun N-terminal kinase activity and AP-1-dependent gene activation. J Biol Chem. 270:8377–8380. 1995. View Article : Google Scholar : PubMed/NCBI

22 

Davison K, Mann KK, Waxman S and Miller WH Jr: JNK activation is a mediator of arsenic trioxide-induced apoptosis in acute promyelocytic leukemia cells. Blood. 103:3496–3502. 2004. View Article : Google Scholar : PubMed/NCBI

23 

Cuadrado A and Nebreda AR: Mechanisms and functions of p38 MAPK signalling. Biochem J. 429:403–417. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Walsh MF, Thamilselvan V, Grotelueschen R, Farhana L and Basson M: Absence of adhesion triggers differential FAK and SAPKp38 signals in SW620 human colon cancer cells that may inhibit adhesiveness and lead to cell death. Cell Physiol Biochem. 13:135–146. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Darnell JE Jr, Kerr IM and Stark GR: Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 264:1415–1421. 1994. View Article : Google Scholar : PubMed/NCBI

26 

Beierle EA, Ma X, Stewart J, Nyberg C, Trujillo A, Cance WG and Golubovskaya VM: Inhibition of focal adhesion kinase decreases tumor growth in human neuroblastoma. Cell Cycle. 9:1005–1015. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Motti ML, De Marco C, Califano D, Fusco A and Viglietto G: Akt-dependent T198 phosphorylation of cyclin-dependent kinase inhibitor p27kip1 in breast cancer. Cell Cycle. 3:1074–1080. 2004. View Article : Google Scholar : PubMed/NCBI

28 

Viglietto G, Motti ML and Fusco A: Understanding p27(kip1) deregulation in cancer: Down-regulation or mislocalization. Cell Cycle. 1:394–400. 2002. View Article : Google Scholar

29 

Pourmand G, Ziaee AA, Abedi AR, Mehrsai A, Alavi HA, Ahmadi A and Saadati HR: Role of PTEN gene in progression of prostate cancer. Urol J. 4:95–100. 2007.PubMed/NCBI

30 

Guertin DA, Stevens DM, Saitoh M, Kinkel S, Crosby K, Sheen JH, Mullholland DJ, Magnuson MA, Wu H and Sabatini DM: mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice. Cancer Cell. 15:148–159. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Yang Z, Yuan XG, Chen J, Luo SW, Luo ZJ and Lu NH: Reduced expression of PTEN and increased PTEN phosphorylation at residue Ser380 in gastric cancer tissues: A novel mechanism of PTEN inactivation. Clin Res Hepatol Gastroenterol. 37:72–79. 2013. View Article : Google Scholar

32 

Robertson BW, Bonsal L and Chellaiah MA: Regulation of Erk1/2 activation by osteopontin in PC3 human prostate cancer cells. Mol Cancer. 9:2602010. View Article : Google Scholar : PubMed/NCBI

33 

Chiang GG and Abraham RT: Phosphorylation of mammalian target of rapamycin (mTOR) at Ser-2448 is mediated by p70S6 kinase. J Biol Chem. 280:25485–25490. 2005. View Article : Google Scholar : PubMed/NCBI

34 

Hong S, Zhao B, Lombard DB, Fingar DC and Inoki K: Crosstalk between sirtuin and mammalian target of rapamycin complex 1 (mTORC1) signaling in the regulation of S6 kinase 1 (S6K1) phosphorylation. J Biol Chem. 289:13132–13141. 2014. View Article : Google Scholar : PubMed/NCBI

35 

Dufner A and Thomas G: Ribosomal S6 kinase signaling and the control of translation. Exp Cell Res. 253:100–109. 1999. View Article : Google Scholar : PubMed/NCBI

36 

Pullen N and Thomas G: The modular phosphorylation and activation of p70s6k. FEBS Lett. 410:78–82. 1997. View Article : Google Scholar : PubMed/NCBI

37 

Pearson RB, Dennis PB, Han JW, Williamson NA, Kozma SC, Wettenhall RE and Thomas G: The principal target of rapamycin-induced p70s6k inactivation is a novel phosphorylation site within a conserved hydrophobic domain. EMBO J. 14:5279–5287. 1995.PubMed/NCBI

38 

Dowling RJ, Topisirovic I, Alain T, Bidinosti M, Fonseca BD, Petroulakis E, Wang X, Larsson O, Selvaraj A, Liu Y, et al: mTORC1-mediated cell proliferation, but not cell growth, controlled by the 4E-BPs. Science. 328:1172–1176. 2010. View Article : Google Scholar : PubMed/NCBI

39 

Sonenberg N and Hinnebusch AG: Regulation of translation initiation in eukaryotes: Mechanisms and biological targets. Cell. 136:731–745. 2009. View Article : Google Scholar : PubMed/NCBI

40 

Kahn BB, Alquier T, Carling D and Hardie DG: AMP-activated protein kinase: Ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 1:15–25. 2005. View Article : Google Scholar : PubMed/NCBI

41 

Mitchelhill KI, Michell BJ, House CM, Stapleton D, Dyck J, Gamble J, Ullrich C, Witters LA and Kemp BE: Posttranslational modifications of the 5′-AMP-activated protein kinase β1 subunit. J Biol Chem. 272:24475–24479. 1997. View Article : Google Scholar : PubMed/NCBI

42 

Ha J, Daniel S, Broyles SS and Kim KH: Critical phosphorylation sites for acetyl-CoA carboxylase activity. J Biol Chem. 269:22162–22168. 1994.PubMed/NCBI

43 

Cantley LC: The phosphoinositide 3-kinase pathway. Science. 296:1655–1657. 2002. View Article : Google Scholar : PubMed/NCBI

44 

Osaki M, Oshimura M and Ito H: PI3K-Akt pathway: Its functions and alterations in human cancer. Apoptosis. 9:667–676. 2004. View Article : Google Scholar : PubMed/NCBI

45 

Akinleye A, Avvaru P, Furqan M, Song Y and Liu D: Phosphatidylinositol 3-kinase (PI3K) inhibitors as cancer therapeutics. J Hematol Oncol. 6:882013. View Article : Google Scholar : PubMed/NCBI

46 

Maira SM, Stauffer F, Brueggen J, Furet P, Schnell C, Fritsch C, Brachmann S, Chène P, De Pover A, Schoemaker K, et al: Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther. 7:1851–1863. 2008. View Article : Google Scholar : PubMed/NCBI

47 

Chanthery YH, Gustafson WC, Itsara M, Persson A, Hackett CS, Grimmer M, Charron E, Yakovenko S, Kim G, Matthay KK, et al: Paracrine signaling through MYCN enhances tumor-vascular interactions in neuroblastoma. Sci Transl Med. 4:115ra32012. View Article : Google Scholar : PubMed/NCBI

48 

Seitz C, Hugle M, Cristofanon S, Tchoghandjian A and Fulda S: The dual PI3K/mTOR inhibitor NVP-BEZ235 and chloroquine synergize to trigger apoptosis via mitochondrial-lysosomal cross-talk. Int J Cancer. 132:2682–2693. 2013. View Article : Google Scholar

49 

Garcia-Echeverria C and Sellers WR: Drug discovery approaches targeting the PI3K/Akt pathway in cancer. Oncogene. 27:5511–5526. 2008. View Article : Google Scholar : PubMed/NCBI

50 

Yu P, Laird AD, Du X, Wu J, Won KA, Yamaguchi K, Hsu PP, Qian F, Jaeger CT, Zhang W, et al: Characterization of the activity of the PI3K/mTOR inhibitor XL765 (SAR245409) in tumor models with diverse genetic alterations impacting the PI3K pathway. Mol Cancer Ther. 13:1078–1091. 2014. View Article : Google Scholar : PubMed/NCBI

51 

Papadopoulos KP, Tabernero J, Markman B, Patnaik A, Tolcher AW, Baselga J, Shi W, Egile C, Ruiz-Soto R, Laird AD, et al: Phase I safety, pharmacokinetic, and pharmacodynamic study of SAR245409 (XL765), a novel, orally administered PI3K/mTOR inhibitor in patients with advanced solid tumors. Clin Cancer Res. 20:2445–2456. 2014. View Article : Google Scholar : PubMed/NCBI

52 

Jänne PA, Cohen RB, Laird AD, Macé S, Engelman JA, Ruiz-Soto R, Rockich K, Xu J, Shapiro GI, Martinez P, et al: Phase I safety and pharmacokinetic study of the PI3K/mTOR inhibitor SAR245409 (XL765) in combination with erlotinib in patients with advanced solid tumors. J Thorac Oncol. 9:316–323. 2014. View Article : Google Scholar : PubMed/NCBI

53 

Li Z, Yan S, Attayan N, Ramalingam S and Thiele CJ: Combination of an allosteric Akt Inhibitor MK-2206 with etoposide or rapamycin enhances the antitumor growth effect in neuroblastoma. Clin Cancer Res. 18:3603–3615. 2012. View Article : Google Scholar : PubMed/NCBI

54 

Johnsen JI, Segerström L, Orrego A, Elfman L, Henriksson M, Kågedal B, Eksborg S, Sveinbjörnsson B and Kogner P: Inhibitors of mammalian target of rapamycin downregulate MYCN protein expression and inhibit neuroblastoma growth in vitro and in vivo. Oncogene. 27:2910–2922. 2008. View Article : Google Scholar

55 

Lee T, Yao G, Nevins J and You L: Sensing and integration of Erk and PI3K signals by Myc. PLOS Comput Biol. 4:e10000132008. View Article : Google Scholar : PubMed/NCBI

56 

Maris JM, Hogarty MD, Bagatell R and Cohn SL: Neuroblastoma. Lancet. 369:2106–2120. 2007. View Article : Google Scholar : PubMed/NCBI

57 

Chesler L, Schlieve C, Goldenberg DD, Kenney A, Kim G, McMillan A, Matthay KK, Rowitch D and Weiss WA: Inhibition of phosphatidylinositol 3-kinase destabilizes Mycn protein and blocks malignant progression in neuroblastoma. Cancer Res. 66:8139–8146. 2006. View Article : Google Scholar : PubMed/NCBI

58 

Duffy DJ, Krstic A, Schwarzl T, Higgins DG and Kolch W: GSK3 inhibitors regulate MYCN mRNA levels and reduce neuroblastoma cell viability through multiple mechanisms, including p53 and Wnt signaling. Mol Cancer Ther. 13:454–467. 2014. View Article : Google Scholar

59 

Otto T, Horn S, Brockmann M, Eilers U, Schüttrumpf L, Popov N, Kenney AM, Schulte JH, Beijersbergen R, Christiansen H, et al: Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma. Cancer Cell. 15:67–78. 2009. View Article : Google Scholar

60 

Yao JE, Yan M, Guan Z, Pan CB, Xia LP, Li CX, Wang LH, Long ZJ, Zhao Y, Li MW, et al: Aurora-A down-regulates IkappaBalpha via Akt activation and interacts with insulin-like growth factor-1 induced phosphatidylinositol 3-kinase pathway for cancer cell survival. Mol Cancer. 8:952009. View Article : Google Scholar : PubMed/NCBI

61 

Levine AJ: p53, the cellular gatekeeper for growth and division. Cell. 88:323–331. 1997. View Article : Google Scholar : PubMed/NCBI

62 

Loughery J, Cox M, Smith LM and Meek DW: Critical role for p53-serine 15 phosphorylation in stimulating transactivation at p53-responsive promoters. Nucleic Acids Res. 42:7666–7680. 2014. View Article : Google Scholar : PubMed/NCBI

63 

Cox ML and Meek DW: Phosphorylation of serine 392 in p53 is a common and integral event during p53 induction by diverse stimuli. Cell Signal. 22:564–571. 2010. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Durbas M, Horwacik I, Boratyn E, Kamycka E and Rokita H: GD2 ganglioside specific antibody treatment downregulates PI3K/Akt/mTOR signaling network in human neuroblastoma cell lines. Int J Oncol 47: 1143-1159, 2015.
APA
Durbas, M., Horwacik, I., Boratyn, E., Kamycka, E., & Rokita, H. (2015). GD2 ganglioside specific antibody treatment downregulates PI3K/Akt/mTOR signaling network in human neuroblastoma cell lines. International Journal of Oncology, 47, 1143-1159. https://doi.org/10.3892/ijo.2015.3070
MLA
Durbas, M., Horwacik, I., Boratyn, E., Kamycka, E., Rokita, H."GD2 ganglioside specific antibody treatment downregulates PI3K/Akt/mTOR signaling network in human neuroblastoma cell lines". International Journal of Oncology 47.3 (2015): 1143-1159.
Chicago
Durbas, M., Horwacik, I., Boratyn, E., Kamycka, E., Rokita, H."GD2 ganglioside specific antibody treatment downregulates PI3K/Akt/mTOR signaling network in human neuroblastoma cell lines". International Journal of Oncology 47, no. 3 (2015): 1143-1159. https://doi.org/10.3892/ijo.2015.3070
Copy and paste a formatted citation
x
Spandidos Publications style
Durbas M, Horwacik I, Boratyn E, Kamycka E and Rokita H: GD2 ganglioside specific antibody treatment downregulates PI3K/Akt/mTOR signaling network in human neuroblastoma cell lines. Int J Oncol 47: 1143-1159, 2015.
APA
Durbas, M., Horwacik, I., Boratyn, E., Kamycka, E., & Rokita, H. (2015). GD2 ganglioside specific antibody treatment downregulates PI3K/Akt/mTOR signaling network in human neuroblastoma cell lines. International Journal of Oncology, 47, 1143-1159. https://doi.org/10.3892/ijo.2015.3070
MLA
Durbas, M., Horwacik, I., Boratyn, E., Kamycka, E., Rokita, H."GD2 ganglioside specific antibody treatment downregulates PI3K/Akt/mTOR signaling network in human neuroblastoma cell lines". International Journal of Oncology 47.3 (2015): 1143-1159.
Chicago
Durbas, M., Horwacik, I., Boratyn, E., Kamycka, E., Rokita, H."GD2 ganglioside specific antibody treatment downregulates PI3K/Akt/mTOR signaling network in human neuroblastoma cell lines". International Journal of Oncology 47, no. 3 (2015): 1143-1159. https://doi.org/10.3892/ijo.2015.3070
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