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 Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
June-2014 Volume 33 Issue 6

Full Size Image

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-2014 Volume 33 Issue 6

Full Size Image

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

Overexpression of Her-2 upregulates FoxM1 in gastric cancer

  • Authors:
    • Weiwei Qi
    • Xiaoxiao Li
    • Yongchun Zhang
    • Ruyong Yao
    • Wensheng Qiu
    • Dongfang Tang
    • Jun Liang
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, The Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong 266003, P.R. China, Central Laboratory, The Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong 266003, P.R. China, Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong 266003, P.R. China
  • Pages: 1531-1538
    |
    Published online on: April 7, 2014
       https://doi.org/10.3892/ijmm.2014.1732
  • 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

The transcription factor, forkhead box protein M1 (FoxM1), and the tyrosine kinase receptor, human epidermal growth factor receptor-2 (Her-2), are aberrantly expressed in a number of human malignancies, and are closely associated with the development of cancer. However, their regulatory mechanisms and their involvement in tumor development have not been extensively investigated, particularly in gastric cancer. In the present study, we examined the expression levels of FoxM1 and Her-2 in samples from patients with gastric cancer, as well as gastric cancer cell lines. Their regulatory mechanisms and the connection between them were also explored. We found that FoxM1 and Her-2 expression was markedly higher in the gastric cancer samples, while a strong association was found between them at the mRNA and protein level. When we regulated the levels of Her-2 in the gastric cancer cell lines, the expression of FoxM1 changed accordingly. Following the transfection of Her-2 expression vectors into the gastric cell lines, the luciferase activity of the FoxM1 promoter positively increased along with the concentration of pcDNA3.1-Her-2. However, Her-2-siRNA inverted this variation, which was further confirmed by treatment with the Her-2 inhibitor, trastuzumab, revealing that Her-2 regulates FoxM1 expression at the promoter level in gastric cancer cells. Our results suggest that FoxM1 and Her-2 are important diagnostic markers for gastric cancer. FoxM1 may be a potential cellular target for therapeutic intervention, particularly in gastric cancers resistant to Her-2-targeted therapy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Wierstra I and Alves J: FOXM1, a typical proliferation-associated transcription factor. Biol Chem. 388:1257–1274. 2007. View Article : Google Scholar : PubMed/NCBI

2 

Ma RY, Tong TH, Leung WY and Yao KM: Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1. Methods Mol Biol. 647:113–123. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Katoh Y and Katoh M: Hedgehog target genes: mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation. Curr Mol Med. 9:873–886. 2009. View Article : Google Scholar : PubMed/NCBI

4 

Wang IC, Chen YJ, Hughes D, Petrovic V, Major ML, Park HJ, Tan Y, Ackerson T and Costa RH: Forkhead box M1 regulates the transcriptional network of genes essential for mitotic progression and genes encoding the SCF (Skp2-Cks1) ubiquitin ligase. Mol Cell Biol. 25:10875–10894. 2005. View Article : Google Scholar : PubMed/NCBI

5 

Costa RH: FoxM1 dances with mitosis. Nat Cell Biol. 7:108–110. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Okada K, Fujiwara Y, Takahashi T, Nakamura Y, Takiguchi S, Nakajima K, Miyata H, Yamasaki M, Kurokawa Y, Mori M and Doki Y: Overexpression of forkhead box M1 transcription factor (FOXM1) is a potential prognostic marker and enhances chemoresistance for docetaxel in gastric cancer. Ann Surg Oncol. 20:1035–1043. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Liu M, Dai B, Kang SH, Ban K, Huang FJ, Lang FF, Aldape KD, Xie TX, Pelloski CE, Xie K, Sawaya R and Huang S: FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells. Cancer Res. 66:3593–3602. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Yau C, Wang Y, Zhang Y, Foekens JA and Benz CC: Young age, increased tumor proliferation and FOXM1 expression predict early metastatic relapse only for endocrine-dependent breast cancers. Breast Cancer Res Treat. 126:803–810. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Kim IM, Ackerson T, Ramakrishna S, Tretiakova M, Wang IC, Kalin TV, Major ML, Gusarova GA, Yoder HM, Costa RH and Kalinichenko VV: The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer. Cancer Res. 66:2153–2161. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Xu N, Zhang X, Wang X, Ge HY, Wang XY, Garfield D, Yang P, Song YL and Bai CX: FoxM1 mediated resistance to gefitinib in non-small-cell lung cancer cells. Acta Pharmacol Sin. 33:675–681. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Kwok JM, Peck B, Monteiro LJ, Schwenen HD, Millour J, Coombes RC, Myatt SS and Lam EW: FOXM1 confers acquired cisplatin resistance in breast cancer cells. Mol Cancer Res. 8:24–34. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Koeppen HK, Wright BD, Burt AD, Quirke P, McNicol AM, Dybdal NO, Sliwkowski MX and Hillan KJ: Overexpression of HER2/neu in solid tumours: an immunohistochemical survey. Histopathology. 38:96–104. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Kaptain S, Tan LK and Chen B: Her-2/neu and breast cancer. Diagn Mol Pathol. 10:139–152. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Hirashima N, Takahashi W, Yoshii S, Yamane T and Ooi A: Protein overexpression and gene amplification of c-erb B-2 in pulmonary carcinomas: a comparative immunohistochemical and fluorescence in situ hybridization study. Mod Pathol. 14:556–562. 2001. View Article : Google Scholar : PubMed/NCBI

15 

Zhang H, Berezov A, Wang Q, Zhang G, Drebin J, Murali R and Greene MI: ErbB receptors: from oncogenes to targeted cancer therapies. J Clin Invest. 117:2051–2058. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Yarden Y and Sliwkowski MX: Untangling the ErbB signalling network. Nat Rev Mol Cell Biol. 2:127–137. 2001. View Article : Google Scholar : PubMed/NCBI

17 

Montemurro F, Valabrega G and Aglietta M: Lapatinib: a dual inhibitor of EGFR and HER2 tyrosine kinase activity. Expert Opin Biol Ther. 7:257–268. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Garcia I, Vizoso F, Martin A, Sanz L, Abdel-Lah O, Raigoso P and Garcia-Muniz JL: Clinical significance of the epidermal growth factor receptor and HER2 receptor in resectable gastric cancer. Ann Surg Oncol. 10:234–241. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Tripathy D, Slamon DJ, Cobleigh M, Arnold A, Saleh M, Mortimer JE, Murphy M and Stewart SJ: Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression. J Clin Oncol. 22:1063–1070. 2004. View Article : Google Scholar : PubMed/NCBI

20 

Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Ruschoff J and Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 376:687–697. 2010. View Article : Google Scholar

21 

Carr JR, Park HJ, Wang Z, Kiefer MM and Raychaudhuri P: FoxM1 mediates resistance to herceptin and paclitaxel. Cancer Res. 70:5054–5063. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Remmele W and Stegner HE: Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe. 8:138–140. 1987.(In German).

23 

Hofmann M, Stoss O, Shi D, Buttner R, van de Vijver M, Kim W, Ochiai A, Ruschoff J and Henkel T: Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 52:797–805. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Huang WY, Sheehy TM, Moore LE, Hsing AW and Purdue MP: Simultaneous recovery of DNA and RNA from formalin-fixed paraffin-embedded tissue and application in epidemiologic studies. Cancer Epidemiol Biomarkers Prev. 19:973–977. 2010. View Article : Google Scholar : PubMed/NCBI

25 

McKenzie SJ, DeSombre KA, Bast BS, Hollis DR, Whitaker RS, Berchuck A, Boyer CM and Bast RC Jr: Serum levels of HER-2 neu (C-erbB-2) correlate with overexpression of p185neu in human ovarian cancer. Cancer. 71:3942–3946. 1993. View Article : Google Scholar : PubMed/NCBI

26 

Dang HZ, Yu Y and Jiao SC: Prognosis of HER2 over-expressing gastric cancer patients with liver metastasis. World J Gastroenterol. 18:2402–2407. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Zhou F, Li N, Jiang W, Hua Z, Xia L, Wei Q and Wang L: Prognosis significance of HER-2/neu overexpression/amplification in Chinese patients with curatively resected gastric cancer after the ToGA clinical trial. World J Surg Oncol. 10:2742012. View Article : Google Scholar : PubMed/NCBI

28 

Halon A, Donizy P, Biecek P, Rudno-Rudzinska J, Kielan W and Matkowski R: HER-2 expression in immunohistochemistry has no prognostic significance in gastric cancer patients. ScientificWorldJournal. 2012:9412592012. View Article : Google Scholar : PubMed/NCBI

29 

Li Q, Zhang N, Jia Z, Le X, Dai B, Wei D, Huang S, Tan D and Xie K: Critical role and regulation of transcription factor FoxM1 in human gastric cancer angiogenesis and progression. Cancer Res. 69:3501–3509. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Guo S and Sonenshein GE: Forkhead box transcription factor FOXO3a regulates estrogen receptor alpha expression and is repressed by the Her-2/neu/phosphatidylinositol 3-kinase/Akt signaling pathway. Mol Cell Biol. 24:8681–8690. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Delpuech O, Griffiths B, East P, Essafi A, Lam EW, Burgering B, Downward J and Schulze A: Induction of Mxi1-SR alpha by FOXO3a contributes to repression of Myc-dependent gene expression. Mol Cell Biol. 27:4917–4930. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Wilson MS, Brosens JJ, Schwenen HD and Lam EW: FOXO and FOXM1 in cancer: the FOXO-FOXM1 axis shapes the outcome of cancer chemotherapy. Curr Drug Targets. 12:1256–1266. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Nahta R and Esteva FJ: HER2 therapy: molecular mechanisms of trastuzumab resistance. Breast Cancer Res. 8:2152006. View Article : Google Scholar : PubMed/NCBI

34 

Bhat UG, Halasi M and Gartel AL: Thiazole antibiotics target FoxM1 and induce apoptosis in human cancer cells. PLoS One. 4:e55922009. View Article : Google Scholar : PubMed/NCBI

35 

Gusarova GA, Wang IC, Major ML, Kalinichenko VV, Ackerson T, Petrovic V and Costa RH: A cell-penetrating ARF peptide inhibitor of FoxM1 in mouse hepatocellular carcinoma treatment. J Clin Invest. 117:99–111. 2007. View Article : Google Scholar : PubMed/NCBI

36 

Radhakrishnan SK, Bhat UG, Hughes DE, Wang IC, Costa RH and Gartel AL: Identification of a chemical inhibitor of the oncogenic transcription factor forkhead box M1. Cancer Res. 66:9731–9735. 2006. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Qi W, Li X, Zhang Y, Yao R, Qiu W, Tang D and Liang J: Overexpression of Her-2 upregulates FoxM1 in gastric cancer. Int J Mol Med 33: 1531-1538, 2014.
APA
Qi, W., Li, X., Zhang, Y., Yao, R., Qiu, W., Tang, D., & Liang, J. (2014). Overexpression of Her-2 upregulates FoxM1 in gastric cancer. International Journal of Molecular Medicine, 33, 1531-1538. https://doi.org/10.3892/ijmm.2014.1732
MLA
Qi, W., Li, X., Zhang, Y., Yao, R., Qiu, W., Tang, D., Liang, J."Overexpression of Her-2 upregulates FoxM1 in gastric cancer". International Journal of Molecular Medicine 33.6 (2014): 1531-1538.
Chicago
Qi, W., Li, X., Zhang, Y., Yao, R., Qiu, W., Tang, D., Liang, J."Overexpression of Her-2 upregulates FoxM1 in gastric cancer". International Journal of Molecular Medicine 33, no. 6 (2014): 1531-1538. https://doi.org/10.3892/ijmm.2014.1732
Copy and paste a formatted citation
x
Spandidos Publications style
Qi W, Li X, Zhang Y, Yao R, Qiu W, Tang D and Liang J: Overexpression of Her-2 upregulates FoxM1 in gastric cancer. Int J Mol Med 33: 1531-1538, 2014.
APA
Qi, W., Li, X., Zhang, Y., Yao, R., Qiu, W., Tang, D., & Liang, J. (2014). Overexpression of Her-2 upregulates FoxM1 in gastric cancer. International Journal of Molecular Medicine, 33, 1531-1538. https://doi.org/10.3892/ijmm.2014.1732
MLA
Qi, W., Li, X., Zhang, Y., Yao, R., Qiu, W., Tang, D., Liang, J."Overexpression of Her-2 upregulates FoxM1 in gastric cancer". International Journal of Molecular Medicine 33.6 (2014): 1531-1538.
Chicago
Qi, W., Li, X., Zhang, Y., Yao, R., Qiu, W., Tang, D., Liang, J."Overexpression of Her-2 upregulates FoxM1 in gastric cancer". International Journal of Molecular Medicine 33, no. 6 (2014): 1531-1538. https://doi.org/10.3892/ijmm.2014.1732
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