Myc lacks E2F1's ability to suppress skin carcinogenesis.
Myc and E2F1 can each stimulate proliferation, induce apoptosis, and contribute to oncogenic transformation. However, only E2F1 has been shown to have a tumor suppressive activity under some conditions. To examine the potential of Myc to suppress tumorigenesis under one of the conditions in which E2F1 functions to suppress tumorigenesis, transgenic mice expressing Myc under the control of a keratin 5 (K5) promoter were generated. Like K5 E2F1 transgenic mice, K5 Myc transgenic mice have hyperplastic and hyperproliferative epidermis and develop spontaneous tumors in the skin and oral epithelium. In addition, K5 Myc and K5 E2F1 transgenic mice both display aberrant, p53-dependent apoptosis in the epidermis. It has been demonstrated that deregulated expression of E2F1 in the epidermis of transgenic mice inhibits tumorigenesis in a two-stage skin carcinogenesis assay. In sharp contrast to those results, deregulated expression of Myc in the epidermis of transgenic mice resulted in an enhanced response to two-stage skin carcinogenesis. We conclude that while Myc and E2F1 have similar proliferative, apoptotic and oncogenic properties in mouse epidermis, Myc lacks E2F1's tumor suppressive property. This suggests that E2F1's unique ability to inhibit skin carcinogenesis is not simply a consequence of promoting p53-dependent apoptosis.
Rounbehler
R J
RJ
University of Texas M.D. Anderson Cancer Center, Science Park Research Division, Park Road 1C, Smithville, Texas 78957, USA.
Schneider-Broussard
R
R
Conti
C J
CJ
Johnson
D G
DG
D000367:Age Factors; D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D001973:Bromodeoxyuridine / Q000378:metabolism; D018797:Cell Cycle Proteins; D002455:Cell Division; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D004817:Epidermis / Q000378:metabolism; D005091:Exons; D016158:Genes, p53 / Q000235:genetics; D020287:In Situ Nick-End Labeling; D053569:Keratin-15; D053555:Keratin-5; D007633:Keratins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism* / Q000502:physiology*; D012878:Skin Neoplasms / Q000209:etiology* / Q000378:metabolism*; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism*; D019076:Transgenes
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D053569:Keratin-15; D053555:Keratin-5; C492053:Krt15 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D007633:Keratins; D001973:Bromodeoxyuridine