cHa-ras proto-oncogene. Amplification and overexpression in UV-B-induced mouse skin papillomas and carcinomas

The role of cellular proto-oncogene activation in shortwave UV light in the B range (UV-B)--induced skin carcinogenesis was investigated. Epidermal papillomas and carcinomas were induced on the depilated skin surface of Sencar mice with single-dose UV-B irradiation (7 x 10(4) J/m2). The tumors thus initiated were present in 18.8% of treated animals and were primarily benign papillomas, while a few (6 of 17) progressed to form squamous cell carcinomas. A 5- to 10-fold stimulation of cHa-ras gene expression in both papillomas and carcinomas was observed. Other cellular proto-oncogenes such as cKi-ras, c-myc, or c-fos specific messenger RNAs were not detected in these UV-B--induced skin tumors. Subsequent Southern blot analysis revealed a threefold to fivefold amplification of cHa-ras gene in skin papillomas and carcinomas. However, only the carcinoma and not the papilloma DNA induced foci in the classic NIH-3T3 transformation assay, suggesting that activation of cHa-ras gene alone is not sufficient to exhibit this phenotypic expression of transformed cells. The NIH-3T3 transformants exhibited (1) anchorage independent growth on soft agar, (2) tumor induction in athymic mice, and (3) overexpression and amplification of the cHa-ras gene. We propose that overexpression of a ras gene by gene amplification plays a role in the UV-B--induced skin carcinogenesis process.