Activation of the cellular harvey ras gene in mouse skin tumors initiated with urethane

✍ Scribed by Keith Bonham; Travis Embry; David Gibson; Debbie R. Jaffe; Robin A. Roberts; Anne E. Cress; G. Tim Bowden

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 637 KB
• Volume: 2
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.2940020106

✦ Synopsis

Mouse skin tumors, benign papillomas, and squamous cell carcinomas (SCCs) were initiated by a single topical application of urethane followed by repeated promotion with 12-0-tetradecanoylphorbol-13-acetate (TPA). Using the NIH 3T3 focus forming assay, dominant transforming activity was detected in DNA isolated from SCC samples. Rearranged and amplified copies o f the C-Ha-fJs gene were detected in NIH 3T3 transformant cell lines, indicating that an activated Ha-ras gene had been transferred t o the NIH 3T3 recipient cells. Analysis of p21ras from the transformant cell lines suggested that the activating ras mutation was present in codon 61. Ultimately, the Ha-ras gene was shown t o be activated by a specific A-;T transversion at the second position of codon 61. This mutation was detected in both benign papillomas and SCCs, suggesting the activation occurred early in tumor development. The results demonstrate a highly consistent activation of the Ha-ras oncogene by a specific point mutation, suggesting a functional role for an activated rasgene in the initiation of mouse skin tumors by urethane.