E2F3a stimulates proliferation, p53-independent apoptosis and carcinogenesis in a transgenic mouse model.
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.
Paulson
Qiwei X
QX
Department of Carcinogenesis, University of Texas MD Anderson Cancer Center, Science Park Research Division, Smithville, Texas 78957, USA.
McArthur
Mark J
MJ
Johnson
David G
DG
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D050699:E2F3 Transcription Factor / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000473:pathology; D006801:Humans; D006965:Hyperplasia; D007438:Introns / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009369:Neoplasms / Q000139:chemically induced / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D050699:E2F3 Transcription Factor; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53