Induction of p53 and melanoma cell death is reciprocal with down-regulation of E2F, cyclin D1 and pRB

Abstract

Tumor-suppressor-gene products such as p53 and retinoblastoma (Rb) play an important role as negative regulators of cell-cycle progression, which is reciprocally favored by the availability of cyclin D1 and the E2F transcription factor. We now show that UV irradiation of B16 melanoma after prior exposure to the radiation sensitizer, bromodeoxyuridine (BUdR) leads to induction of p53 and DNA fragmentation, and concomitant decreases in Rb, E2F, cyclin D1, and cell viability, with no comparable effects on irradiated unsensitized cells. Our data suggest that over-expression of p53 correlates with down-regulation of E2F, cyclin D1 in inducing apoptosis.