The Possible Role of E2F in Rat Mammary Carcinogenesis
Abstract
Upregulation of the E2F family of transcription factors has been suggested to be commonly associated with a neoplastic phenotype. To understand the consequences of altered E2F activity in cancer, I have used two model systems: a rat mammary tumor assay and an NIH 3T3 focus formation assay. While the rat mammary study did not yield conclusive results, the tissue culture assay revealed that E2F transcription factors are not oncogenic in NIH 3T3 cells. Rather, over expression of E2F1, E2F2, and E2F3 caused a dramatic decrease in foci induced by the activated c-Ha-ras oncogene. This inhibition of ras-mediated transformation was dependent upon E2F DNA binding activity but did not require amino or carboxy terminal E2F1 protein interaction domains. I have found that introduction of exogenous E2F1 into NIH 3T3 cells previously transformed by ras was less growth inhibitory than was E2F1 in untransformed NIH 3T3 cells, suggesting that neoplastic transformation can partially overcome the inhibitory effects of E2F1. However, ras transformed cells remain sensitive to the inhibitory effects of E2F2 and E2F3. I am currently investigating if E2F can inhibit transformation mediated by oncogene other than the ras oncogene.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA372358
Entities
People
- Peggy J. Farnham
- Traci Lee
Organizations
- University of Wisconsin–Madison