HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Cellular transformation of mouse embryo fibroblasts in the absence of activator E2Fs.

AbstractUNLABELLED:
The E2F family of transcription factors, broadly divided into activator and repressor E2Fs, regulates cell cycle genes. Current models indicate that activator E2Fs are necessary for cell cycle progression and tumorigenesis and are also required to mediate transformation induced by DNA tumor viruses. E2Fs are negatively regulated by the retinoblastoma (RB) family of tumor suppressor proteins, and virus-encoded oncogenes disrupt the RB-E2F repressor complexes. This results in the release of activator E2Fs and induction of E2F-dependent genes. In agreement, expression of large tumor T antigens (TAg) encoded by polyomaviruses in mammalian cells results in increased transcriptional levels of E2F target genes. In addition, tumorigenesis induced by transgenic expression of simian virus 40 (SV40) TAg in choroid plexus or intestinal villi requires at least one activator E2F. In contrast, we show that SV40 TAg-induced transformation in mouse embryonic fibroblasts is independent of activator E2Fs. This work, coupled with recent studies showing that proliferation in stem and progenitor cells is independent of activator E2Fs, suggests the presence of parallel pathways governing cell proliferation and tumorigenesis.
IMPORTANCE:
The RB-E2F pathway is altered in many cancers and is also targeted by DNA tumor viruses. Viral oncoprotein action on RBs results in the release of activator E2Fs and upregulation of E2F target genes; thus, activator E2Fs are considered essential for normal and tumorigenic cell proliferation. However, we have observed that SV40 large T antigen can induce cell proliferation and transformation in the absence of activator E2Fs. Our results also suggest that TAg action on pRBs regulates both E2F-dependent and -independent pathways that govern proliferation. Thus, specific cell proliferation pathways affected by RB alterations in cancer may be a factor in tumor behavior and response to therapy.
AuthorsTushar Gupta, Maria Teresa Sáenz Robles, James M Pipas
JournalJournal of virology (J Virol) Vol. 89 Issue 9 Pg. 5124-33 (May 2015) ISSN: 1098-5514 [Electronic] United States
PMID25717106 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2015, American Society for Microbiology. All Rights Reserved.
Chemical References
  • Antigens, Viral, Tumor
  • E2F Transcription Factors
Topics
  • Animals
  • Antigens, Viral, Tumor (genetics, metabolism)
  • Cell Proliferation
  • Cell Transformation, Viral
  • E2F Transcription Factors (metabolism)
  • Fibroblasts (virology)
  • Mice
  • Simian virus 40 (physiology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: