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
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
April 2013 Volume 29 Issue 4

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
April 2013 Volume 29 Issue 4

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

Reactive oxygen species regulate FSH-induced expression of vascular endothelial growth factor via Nrf2 and HIF1α signaling in human epithelial ovarian cancer

  • Authors:
    • Zhenbo Zhang
    • Qianqian Wang
    • Jie Ma
    • Xiaofang Yi
    • Yaping Zhu
    • Xiaowei Xi
    • Youji Feng
    • Zhijun Jin
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, P.R. China, Department of Obstetrics and Gynecology, Changzheng Hospital, The Second Military Medical University, Shanghai, P.R. China, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, P.R. China
  • Pages: 1429-1434
    |
    Published online on: February 6, 2013
       https://doi.org/10.3892/or.2013.2278
  • 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

Follicle-stimulating hormone (FSH) and the FSH receptor contribute to tumor angiogenesis and are acknowledged risk factors for ovarian epithelial cancer (OEC). Accumulating evidence suggests that FSH can induce vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1α (HIF1α) expression. We previously demonstrated that FSH induces reactive oxygen species (ROS) production and activates Nrf2 signaling. This study was performed to investigate whether FSH induces VEGF expression via a ROS-mediated Nrf2 signaling pathway. In the current study, OET cells were treated with FSH; dichlorofluorescein staining was used to determine ROS generation, western blotting was used to quantify Nrf2 expression and VEGF expression was measured using an ELISA. Nrf2 and HIF1α were knocked down using siRNAs to investigate the role of the Nrf2 and HIF1α signaling pathways in FSH-induced VEGF expression. The chromatin immunoprecipitation assay (ChIP) was used to determine HIF1α binding to the VEGF promoter. Finally, it was found that FSH induced ROS production and activated Nrf2 signaling; elimination of ROS or knockdown of Nrf2 blocked FSH-induced VEGF expression. Knockdown of Nrf2 impaired HIF1α signaling activation. Blockage of the FSH-ROS-Nrf2-HIF1α signaling pathway attenuated FSH-induced binding of HIF1α to the VEGF promoter. Collectively, this study indicates that ROS and aberrant expression of Nrf2 play an important role in FSH-induced angiogenesis in OEC, and provides insight into the mechanisms of FSH-induced VEGF expression. Elimination of ROS or inhibition of Nrf2 may represent potential therapeutic targets for the treatment of ovarian cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Wang J, Luo F, Lu JJ, Chen PK, Liu P and Zheng W: VEGF expression and enhanced production by gonadotropins in ovarian epithelial tumors. Int J Cancer. 97:163–167. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Lee B, Kim KH, Jung HJ and Kwon HJ: Matairesinol inhibits angiogenesis via suppression of mitochondrial reactive oxygen species. Biochem Biophys Res Commun. 421:76–80. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Sauer H and Wartenberg M: Reactive oxygen species as signaling molecules in cardiovascular differentiation of embryonic stem cells and tumor-induced angiogenesis. Antioxid Redox Signal. 7:1423–1434. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Ushio-Fukai M and Alexander RW: Reactive oxygen species as mediators of angiogenesis signaling: role of NAD(P)H oxidase. Mol Cell Biochem. 264:85–97. 2004. View Article : Google Scholar : PubMed/NCBI

5 

Ushio-Fukai M and Nakamura Y: Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Lett. 266:37–52. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Xia C, Meng Q, Liu LZ, Rojanasakul Y, Wang XR and Jiang BH: Reactive oxygen species regulate angiogenesis and tumor growth through vascular endothelial growth factor. Cancer Res. 67:10823–10830. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Aljhni R, Ibrahim F, Guillaume YC and Andre C: Reactive oxygen species and nitric oxide effect on the steroid hormone binding with serum albumin. J Pharm Biomed Anal. 62:129–134. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Tada H, Nakashima A, Awaya A, et al: Effects of thymic hormone on reactive oxygen species-scavengers and renal function in tacrolimus-induced nephrotoxicity. Life Sci. 70:1213–1223. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Choi JS, Paek AR, Kim SY and You HJ: GIPC mediates the generation of reactive oxygen species and the regulation of cancer cell proliferation by insulin-like growth factor-1/IGF-1R signaling. Cancer Lett. 294:254–263. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Liu LZ, Hu XW, Xia C, et al: Reactive oxygen species regulate epidermal growth factor-induced vascular endothelial growth factor and hypoxia-inducible factor-1alpha expression through activation of AKT and P70S6K1 in human ovarian cancer cells. Free Radic Biol Med. 41:1521–1533. 2006. View Article : Google Scholar

11 

Okoh V, Deoraj A and Roy D: Estrogen-induced reactive oxygen species-mediated signalings contribute to breast cancer. Biochim Biophys Acta. 1815:115–133. 2011.PubMed/NCBI

12 

Shkolnik K, Tadmor A, Ben-Dor S, Nevo N, Galiani D and Dekel N: Reactive oxygen species are indispensable in ovulation. Proc Natl Acad Sci USA. 108:1462–1467. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Chen W, Sun Z, Wang XJ, et al: Direct interaction between Nrf2 and p21(Cip1/WAF1) upregulates the Nrf2-mediated antioxidant response. Mol Cell. 34:663–673. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Sun Z, Chin YE and Zhang DD: Acetylation of Nrf2 by p300/CBP augments promoter-specific DNA binding of Nrf2 during the antioxidant response. Mol Cell Biol. 29:2658–2672. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Sun Z, Wu T, Zhao F, Lau A, Birch CM and Zhang DD: KPNA6 (Importin {alpha}7)-mediated nuclear import of Keap1 represses the Nrf2-dependent antioxidant response. Mol Cell Biol. 31:1800–1811. 2012.

16 

Villeneuve NF, Lau A and Zhang DD: Regulation of the Nrf2-Keap1 antioxidant response by the ubiquitin proteasome system: an insight into cullin-ring ubiquitin ligases. Antioxid Redox Signal. 13:1699–1712. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Wang XJ, Sun Z, Chen W, Eblin KE, Gandolfi JA and Zhang DD: Nrf2 protects human bladder urothelial cells from arsenite and monomethylarsonous acid toxicity. Toxicol Appl Pharmacol. 225:206–213. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Wang XJ, Sun Z, Villeneuve NF, et al: Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2. Carcinogenesis. 29:1235–1243. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Kim TH, Hur EG, Kang SJ, et al: NRF2 blockade suppresses colon tumor angiogenesis by inhibiting hypoxia-induced activation of HIF-1α. Cancer Res. 71:2260–2275. 2010.PubMed/NCBI

20 

Cascio S, D’Andrea A, Ferla R, et al: miR-20b modulates VEGF expression by targeting HIF-1 alpha and STAT3 in MCF-7 breast cancer cells. J Cell Physiol. 224:242–249. 2010.PubMed/NCBI

21 

Horiuchi A, Imai T, Shimizu M, et al: Hypoxia-induced changes in the expression of VEGF, HIF-1 alpha and cell cycle-related molecules in ovarian cancer cells. Anticancer Res. 22:2697–2702. 2002.PubMed/NCBI

22 

Wong C, Wellman TL and Lounsbury KM: VEGF and HIF-1alpha expression are increased in advanced stages of epithelial ovarian cancer. Gynecol Oncol. 91:513–517. 2003. View Article : Google Scholar : PubMed/NCBI

23 

Huang Y, Hua K, Zhou X, et al: Activation of the PI3K/AKT pathway mediates FSH-stimulated VEGF expression in ovarian serous cystadenocarcinoma. Cell Res. 18:780–791. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Lee J, Park SY, Lee EK, et al: Activation of hypoxia-inducible factor-1alpha is necessary for lysophosphatidic acid-induced vascular endothelial growth factor expression. Clin Cancer Res. 12:6351–6358. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Finkel T: Oxidant signals and oxidative stress. Curr Opin Cell Biol. 15:247–254. 2003. View Article : Google Scholar : PubMed/NCBI

26 

Finkel T: Redox-dependent signal transduction. FEBS Lett. 476:52–54. 2000. View Article : Google Scholar : PubMed/NCBI

27 

Griendling KK and Ushio-Fukai M: Reactive oxygen species as mediators of angiotensin II signaling. Regul Pept. 91:21–27. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Dimmeler S and Zeiher AM: Reactive oxygen species and vascular cell apoptosis in response to angiotensin II and pro-atherosclerotic factors. Regul Pept. 90:19–25. 2000. View Article : Google Scholar : PubMed/NCBI

29 

Frank GD, Eguchi S, Yamakawa T, Tanaka S, Inagami T and Motley ED: Involvement of reactive oxygen species in the activation of tyrosine kinase and extracellular signal-regulated kinase by angiotensin II. Endocrinology. 141:3120–3126. 2000.PubMed/NCBI

30 

Hannken T, Schroeder R, Zahner G, Stahl RA and Wolf G: Reactive oxygen species stimulate p44/42 mitogen-activated protein kinase and induce p27(Kip1): role in angiotensin II-mediated hypertrophy of proximal tubular cells. J Am Soc Nephrol. 11:1387–1397. 2000.PubMed/NCBI

31 

Itoh K, Ishii T, Wakabayashi N and Yamamoto M: Regulatory mechanisms of cellular response to oxidative stress. Free Radic Res. 31:319–324. 1999. View Article : Google Scholar : PubMed/NCBI

32 

Kensler TW, Wakabayashi N and Biswal S: Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol. 47:89–116. 2007. View Article : Google Scholar : PubMed/NCBI

33 

Zhang DD: Mechanistic studies of the Nrf2-Keap1 signaling pathway. Drug Metab Rev. 38:769–789. 2006. View Article : Google Scholar : PubMed/NCBI

34 

Liao H, Zhou Q, Zhang Z, et al: NRF2 is overexpressed in ovarian epithelial carcinoma and is regulated by gonadotrophin and sex-steroid hormones. Oncol Rep. 27:1918–1924. 2012.PubMed/NCBI

35 

Zhou Q, Liu LZ, Fu B, et al: Reactive oxygen species regulate insulin-induced VEGF and HIF-1alpha expression through the activation of p70S6K1 in human prostate cancer cells. Carcinogenesis. 28:28–37. 2007. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang Z, Wang Q, Ma J, Yi X, Zhu Y, Xi X, Feng Y and Jin Z: Reactive oxygen species regulate FSH-induced expression of vascular endothelial growth factor via Nrf2 and HIF1α signaling in human epithelial ovarian cancer. Oncol Rep 29: 1429-1434, 2013.
APA
Zhang, Z., Wang, Q., Ma, J., Yi, X., Zhu, Y., Xi, X. ... Jin, Z. (2013). Reactive oxygen species regulate FSH-induced expression of vascular endothelial growth factor via Nrf2 and HIF1α signaling in human epithelial ovarian cancer. Oncology Reports, 29, 1429-1434. https://doi.org/10.3892/or.2013.2278
MLA
Zhang, Z., Wang, Q., Ma, J., Yi, X., Zhu, Y., Xi, X., Feng, Y., Jin, Z."Reactive oxygen species regulate FSH-induced expression of vascular endothelial growth factor via Nrf2 and HIF1α signaling in human epithelial ovarian cancer". Oncology Reports 29.4 (2013): 1429-1434.
Chicago
Zhang, Z., Wang, Q., Ma, J., Yi, X., Zhu, Y., Xi, X., Feng, Y., Jin, Z."Reactive oxygen species regulate FSH-induced expression of vascular endothelial growth factor via Nrf2 and HIF1α signaling in human epithelial ovarian cancer". Oncology Reports 29, no. 4 (2013): 1429-1434. https://doi.org/10.3892/or.2013.2278
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Z, Wang Q, Ma J, Yi X, Zhu Y, Xi X, Feng Y and Jin Z: Reactive oxygen species regulate FSH-induced expression of vascular endothelial growth factor via Nrf2 and HIF1α signaling in human epithelial ovarian cancer. Oncol Rep 29: 1429-1434, 2013.
APA
Zhang, Z., Wang, Q., Ma, J., Yi, X., Zhu, Y., Xi, X. ... Jin, Z. (2013). Reactive oxygen species regulate FSH-induced expression of vascular endothelial growth factor via Nrf2 and HIF1α signaling in human epithelial ovarian cancer. Oncology Reports, 29, 1429-1434. https://doi.org/10.3892/or.2013.2278
MLA
Zhang, Z., Wang, Q., Ma, J., Yi, X., Zhu, Y., Xi, X., Feng, Y., Jin, Z."Reactive oxygen species regulate FSH-induced expression of vascular endothelial growth factor via Nrf2 and HIF1α signaling in human epithelial ovarian cancer". Oncology Reports 29.4 (2013): 1429-1434.
Chicago
Zhang, Z., Wang, Q., Ma, J., Yi, X., Zhu, Y., Xi, X., Feng, Y., Jin, Z."Reactive oxygen species regulate FSH-induced expression of vascular endothelial growth factor via Nrf2 and HIF1α signaling in human epithelial ovarian cancer". Oncology Reports 29, no. 4 (2013): 1429-1434. https://doi.org/10.3892/or.2013.2278
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