Myc lacks E2F1's ability to suppress skin carcinogenesis

Myc and E2F1 can each stimulate proliferation, induce apoptosis, and contri bute to oncogenic transformation. However, only E2F1 has been shown to have a tumor suppressive activity under some conditions. To examine the potenti al of Myc to suppress tumorigenesis under one of the conditions in which E2 F1 functions to suppress tumorigenesis, transgenic mice expressing Myc unde r the control of a keratin 5 (K5) promoter were generated. Like K5 E2F1 tra nsgenic mice, K5 Myc transgenic mice have hyperplastic and hyperproliferati ve epidermis and develop spontaneous tumors in the skin and oral epithelium . In addition, K5 Myc and K5 E2F1 transgenic mice both display aberrant, p5 3-dependent apoptosis in the epidermis. It has been demonstrated that dereg ulated expression of E2F1 in the epidermis of transgenic mice inhibits tumo rigenesis in a two-stage skin carcinogenesis assay. In sharp contrast to th ose results, deregulated expression of Myc in the epidermis of transgenic m ice resulted in an enhanced response to two-stage skin carcinogenesis. We c onclude that while Myc and E2F1 have similar proliferative, apoptotic and o ncogenic properties in mouse epidermis, Myc lacks E2F1's tumor suppressive property. This suggests that E2F1's unique ability to inhibit skin carcinog enesis is not simply a consequence of promoting p53-dependent apoptosis.