CHA-RAS PROTOONCOGENE - 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 × 104 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. © 1990, American Medical Association. All rights reserved.