Upregulation of E2F transcription factors in chemically induced mouse skintumors

E2F family of transcription factors plays an important role in cell cycle r egulation, oncogenesis and differentiation. E2Fs are a family of heterodime ric transcription factors composed of E2F-like and DP-like subunits. They r egulate expression of specific genes controlling cellular proliferation by binding to specific sequences within the promoter regions of these target g enes and affecting their transcription in a cell cycle dependent manner. Re cent studies have suggested an essential role of Rb/E2F pathway in the pass age of cells through the G1 phase of the cell cycle. To better understand t he role of these transcription factors in epithelial tumorigenesis, we comp ared the expression of various proteins involved in the Rb/E2F pathway in e pidermis and 7,12-dimethylbenz(alpha)anthracene (DMBA)-initiated and 12-O-t etradecanoylphorbol-13-acetate (TPA) promoted papillomas on SENCAR mouse sk in. Western blot analysis data showed 3.0- to 7.6-fold upregulation of E2F- 1, E2F-2, E2F-3, E2F-4 and E2F-5 in tumors compared to normal epidermis. In tumors, the protein expression of DP-1 did not show significant change whe reas that of DP-2 showed a 2.2-fold increase. Compared to normal epidermis, a significant upregulation of pRb (6.3-fold) and p107 (13-fold) was also o bserved in tumors. The protein expression of p130 was not detectable either in normal epidermis or in tumors. These data suggest that the overexpressi on of E2F proteins may be involved in the G1-S phase dysregulation that occ urs during mouse skin tumorigenesis.