E2F3a stimulates proliferation, p53-independent apoptosis and carcinogenesis in a transgenic mouse model

Qiwei X. Paulson, Mark J. McArthur, David G. Johnson

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Mutation or inactivation of the retinoblastoma (Rb) tumor suppressor occurs in most human tumors and results in the deregulation of several members of the E2F family of transcription factors. Among the E2F family, E2F3 has been implicated as a key regulator of cell proliferation and E2F3 gene amplification and overexpression is detected in some human tumors. To study the role of E2F3 in tumor development, we established a transgenic mouse model expressing E2F3a in a number of epithelial tissues via a keratin 5 (K5) promoter. Transgenic expression of E2F3a leads to hyperproliferation, hyperplasia and increased levels of p53-independent apoptosis in transgenic epidermis. Consistent with data from human cancers, the E2F3a transgene is found to have a weak oncogenic activity on its own and to significantly enhance the response to a skin carcinogenesis protocol. The phenotype of K5 E2F3a transgenic mice is distinct from similar transgenic mice expressing E2F1 or E2F4. In particular, E2F3a has a unique apoptotic activity and lacks the tumor suppressive property of E2F1 in this model system.

Original languageEnglish (US)
Pages (from-to)184-190
Number of pages7
JournalCell Cycle
Volume5
Issue number2
DOIs
StatePublished - Jan 16 2006

Keywords

  • Apoptosis
  • Cell cycle
  • E2F3
  • Skin carcinogenesis
  • Transgenic mouse

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Fingerprint

Dive into the research topics of 'E2F3a stimulates proliferation, p53-independent apoptosis and carcinogenesis in a transgenic mouse model'. Together they form a unique fingerprint.

Cite this