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
September-2014 Volume 32 Issue 3

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
September-2014 Volume 32 Issue 3

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

E2F1 acts as a negative feedback regulator of c-Myc‑induced hTERT transcription during tumorigenesis

  • Authors:
    • Yafei Zhang
    • Anran Zhang
    • Caifei Shen
    • Bicheng Zhang
    • Zhiguo Rao
    • Rongquan Wang
    • Shiming Yang
    • Shoubin Ning
    • Gaoping Mao
    • Dianchun Fang
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, P.R. China, Department of Oncology, Wuhan General Hospital of Guangzhou Command, People's Liberation Army, Wuhan, P.R. China, Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, P.R. China, Department of Gastroenterology, Air Force General Hospital of Chinese PLA, Beijing, P.R. China
  • Pages: 1273-1280
    |
    Published online on: June 24, 2014
       https://doi.org/10.3892/or.2014.3287
  • 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

Since induction of hTERT expression and subsequent telomerase activation play a critical role in the multistep process of tumorigenesis, a better understanding of hTERT regulation may provide not only a rationale for the molecular basis of cancer progression but also a path to the development of cancer prevention. The c-Myc oncoprotein can function effectively in activating the transcriptional expression of hTERT through E-box elements on its promoter. E2F transcription factor 1 (E2F1) was found to be a repressor of hTERT transcription by directly binding to its promoter, thereby inhibiting hTERT protein expression. For the extensively crosstalk between c-Myc and E2F1 signals, which is now known to be vital to cell fate, we speculated that E2F1 may play a negative regulatory role in c-Myc-induced hTERT transcription. In the present study, we chose to use human embryonic fibroblast cells as an experimental model system, and present evidence that the E2F1 transcription factor constitutes a negative regulatory system to limit c-Myc transcriptional activation of hTERT in normal cells. Furthermore, we demonstrated that upregulation of the miR-17-92 cluster (miR-20a/miR-17-5p) is involved in the regulation of E2F1-mediated negative feedback of the c-Myc/hTERT pathway. Our results not only reveal novel insights into how normal cells control the transmission of c-Myc-mediated oncogenic signals, but also further establish E2F1 as an important molecular target for cancer therapy.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Wojtyla A, Gladych M and Rubis B: Human telomerase activity regulation. Mol Biol Rep. 38:3339–3349. 2011. View Article : Google Scholar

2 

Harley CB: Telomerase and cancer therapeutics. Nat Rev Cancer. 8:167–179. 2008. View Article : Google Scholar

3 

Kim NW, Piatyszek MA, Prowse KR, et al: Specific association of human telomerase activity with immortal cells and cancer. Science. 266:2011–2015. 1994. View Article : Google Scholar : PubMed/NCBI

4 

Stewart SA and Weinberg RA: Telomeres: cancer to human aging. Annu Rev Cell Dev Biol. 22:531–557. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Land H, Parada LF and Weinberg RA: Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 304:596–602. 1983. View Article : Google Scholar : PubMed/NCBI

6 

Wu KJ, Grandori C, Amacker M, et al: Direct activation of TERT transcription by c-MYC. Nat Genet. 21:220–224. 1999. View Article : Google Scholar : PubMed/NCBI

7 

Greenberg RA, O’Hagan RC, Deng H, et al: Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation. Oncogene. 18:1219–1226. 1999. View Article : Google Scholar : PubMed/NCBI

8 

Kyo S, Takakura M, Fujiwara T and Inoue M: Understanding and exploiting hTERT promoter regulation for diagnosis and treatment of human cancers. Cancer Sci. 99:1528–1538. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Matsumura I, Tanaka H and Kanakura Y: E2F1 and c-Myc in cell growth and death. Cell Cycle. 2:333–338. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Coller HA, Forman JJ and Legesse-Miller A: ‘Myc’ed messages’: myc induces transcription of E2F1 while inhibiting its translation via a microRNA polycistron. PLoS Genet. 3:e1462007.

11 

Crowe DL, Nguyen DC, Tsang KJ and Kyo S: E2F-1 represses transcription of the human telomerase reverse transcriptase gene. Nucleic Acids Res. 29:2789–2794. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Won J, Chang S, Oh S and Kim TK: Small-molecule-based identification of dynamic assembly of E2F-pocket protein-histone deacetylase complex for telomerase regulation in human cells. Proc Natl Acad Sci USA. 101:11328–11333. 2004. View Article : Google Scholar

13 

Lacerte A, Korah J, Roy M, Yang XJ, Lemay S and Lebrun JJ: Transforming growth factor-beta inhibits telomerase through SMAD3 and E2F transcription factors. Cell Signal. 20:50–59. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar

15 

O’Donnell KA, Wentzel EA, Zeller KI, Dang CV and Mendell JT: c-Myc-regulated microRNAs modulate E2F1 expression. Nature. 435:839–843. 2005.PubMed/NCBI

16 

He L, Thomson JM, Hemann MT, et al: A microRNA polycistron as a potential human oncogene. Nature. 435:828–833. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Nagel S, Venturini L, Przybylski GK, et al: Activation of miR-17-92 by NK-like homeodomain proteins suppresses apoptosis via reduction of E2F1 in T-cell acute lymphoblastic leukemia. Leuk Lymphoma. 50:101–108. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Chang TC, Yu D, Lee YS, et al: Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet. 40:43–50. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Sylvestre Y, De Guire V, Querido E, et al: An E2F/miR-20a autoregulatory feedback loop. J Biol Chem. 282:2135–2143. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Li Y, Li Y, Zhang H and Chen Y: MicroRNA-mediated positive feedback loop and optimized bistable switch in a cancer network involving miR-17-92. PLoS One. 6:e263022011. View Article : Google Scholar : PubMed/NCBI

21 

Wong JV, Yao G, Nevins JR and You L: Viral-mediated noisy gene expression reveals biphasic E2f1 response to MYC. Mol Cell. 41:275–285. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Aguda BD, Kim Y, Piper-Hunter MG, Friedman A and Marsh CB: MicroRNA regulation of a cancer network: consequences of the feedback loops involving miR-17-92, E2F, and Myc. Proc Natl Acad Sci USA. 105:19678–19683. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Liang GP, Luo XD and Yang ZC: Influence of human telomerase reverse transcriptase gene transfection on the proliferation of human embryonic fibroblasts. Zhonghua Shao Shang Za Zhi. 21:30–32. 2005.(In Chinese).

24 

Yang SM, Fang DC, Yang JL, Chen L, Luo YH and Liang GP: Antisense human telomerase reverse transcriptase could partially reverse malignant phenotypes of gastric carcinoma cell line in vitro. Eur J Cancer Prev. 17:209–217. 2008. View Article : Google Scholar

25 

Zhang YF, Li XH, Shi YQ, et al: CIAPIN1 confers multidrug resistance through up-regulation of MDR-1 and Bcl-L in LoVo/Adr cells and is independent of p53. Oncol Rep. 25:1091–1098. 2011.PubMed/NCBI

26 

McNabb DS, Reed R and Marciniak RA: Dual luciferase assay system for rapid assessment of gene expression in Saccharomyces cerevisiae. Eukaryot Cell. 4:1539–1549. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

28 

Rounbehler RJ, Rogers PM, Conti CJ and Johnson DG: Inactivation of E2f1 enhances tumorigenesis in a Myc transgenic model. Cancer Res. 62:3276–3281. 2002.PubMed/NCBI

29 

Rounbehler RJ, Schneider-Broussard R, Conti CJ and Johnson DG: Myc lacks E2F1’s ability to suppress skin carcinogenesis. Oncogene. 20:5341–5349. 2001.

30 

Baudino TA, Maclean KH, Brennan J, et al: Myc-mediated proliferation and lymphomagenesis, but not apoptosis, are compromised by E2f1 loss. Mol Cell. 11:905–914. 2003. View Article : Google Scholar : PubMed/NCBI

31 

Conner EA, Lemmer ER, Sánchez A, Factor VM and Thorgeirsson SS: E2F1 blocks and c-Myc accelerates hepatic ploidy in transgenic mouse models. Biochem Biophys Res Commun. 302:114–120. 2003. View Article : Google Scholar : PubMed/NCBI

32 

Engelmann D and Pützer BM: The dark side of E2F1: in transit beyond apoptosis. Cancer Res. 72:571–575. 2012. View Article : Google Scholar : PubMed/NCBI

33 

Polager S and Ginsberg D: p53 and E2f: partners in life and death. Nat Rev Cancer. 9:738–748. 2009. View Article : Google Scholar : PubMed/NCBI

34 

Wu Z and Yu Q: E2F1-mediated apoptosis as a target of cancer therapy. Curr Mol Pharmacol. 2:149–160. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Leone G, Sears R, Huang E, et al: Myc requires distinct E2F activities to induce S phase and apoptosis. Mol Cell. 8:105–113. 2001. View Article : Google Scholar : PubMed/NCBI

36 

Herold S, Herkert B and Eilers M: Facilitating replication under stress: an oncogenic function of MYC? Nat Rev Cancer. 9:441–444. 2009. View Article : Google Scholar : PubMed/NCBI

37 

Park JK, Chung YM, Kang S, et al: c-Myc exerts a protective function through ornithine decarboxylase against cellular insults. Mol Pharmacol. 62:1400–1408. 2002. View Article : Google Scholar : PubMed/NCBI

38 

Lü MH, Liao ZL, Zhao XY, et al: hTERT-based therapy: A universal anticancer approach (Review). Oncol Rep. 28:1945–1952. 2012.PubMed/NCBI

39 

Olive V, Jiang I and He L: mir-17–92, a cluster of miRNAs in the midst of the cancer network. Int J Biochem Cell Biol. 42:1348–1354. 2010.

40 

Zhang Y and Fang D, Yang S and Fang D: E2F1: a potential negative regulator of hTERT transcription in normal cells upon activation of oncogenic c-Myc. Med Sci Monit. 18:RA12–RA15. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang Y, Zhang A, Shen C, Zhang B, Rao Z, Wang R, Yang S, Ning S, Mao G, Fang D, Fang D, et al: E2F1 acts as a negative feedback regulator of c-Myc‑induced hTERT transcription during tumorigenesis. Oncol Rep 32: 1273-1280, 2014.
APA
Zhang, Y., Zhang, A., Shen, C., Zhang, B., Rao, Z., Wang, R. ... Fang, D. (2014). E2F1 acts as a negative feedback regulator of c-Myc‑induced hTERT transcription during tumorigenesis. Oncology Reports, 32, 1273-1280. https://doi.org/10.3892/or.2014.3287
MLA
Zhang, Y., Zhang, A., Shen, C., Zhang, B., Rao, Z., Wang, R., Yang, S., Ning, S., Mao, G., Fang, D."E2F1 acts as a negative feedback regulator of c-Myc‑induced hTERT transcription during tumorigenesis". Oncology Reports 32.3 (2014): 1273-1280.
Chicago
Zhang, Y., Zhang, A., Shen, C., Zhang, B., Rao, Z., Wang, R., Yang, S., Ning, S., Mao, G., Fang, D."E2F1 acts as a negative feedback regulator of c-Myc‑induced hTERT transcription during tumorigenesis". Oncology Reports 32, no. 3 (2014): 1273-1280. https://doi.org/10.3892/or.2014.3287
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Y, Zhang A, Shen C, Zhang B, Rao Z, Wang R, Yang S, Ning S, Mao G, Fang D, Fang D, et al: E2F1 acts as a negative feedback regulator of c-Myc‑induced hTERT transcription during tumorigenesis. Oncol Rep 32: 1273-1280, 2014.
APA
Zhang, Y., Zhang, A., Shen, C., Zhang, B., Rao, Z., Wang, R. ... Fang, D. (2014). E2F1 acts as a negative feedback regulator of c-Myc‑induced hTERT transcription during tumorigenesis. Oncology Reports, 32, 1273-1280. https://doi.org/10.3892/or.2014.3287
MLA
Zhang, Y., Zhang, A., Shen, C., Zhang, B., Rao, Z., Wang, R., Yang, S., Ning, S., Mao, G., Fang, D."E2F1 acts as a negative feedback regulator of c-Myc‑induced hTERT transcription during tumorigenesis". Oncology Reports 32.3 (2014): 1273-1280.
Chicago
Zhang, Y., Zhang, A., Shen, C., Zhang, B., Rao, Z., Wang, R., Yang, S., Ning, S., Mao, G., Fang, D."E2F1 acts as a negative feedback regulator of c-Myc‑induced hTERT transcription during tumorigenesis". Oncology Reports 32, no. 3 (2014): 1273-1280. https://doi.org/10.3892/or.2014.3287
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