Oncogene amplification during tumorigenesis of established rat fibroblasts reversibly transformed by activated human ras oncogenes.

AUTOR(ES)

Winter, E

RESUMO

Normal rat fibroblasts of the established cell line Rat 4 were cotransformed with activated human ras oncogenes and with a cloned chicken thymidine kinase (tk) gene. Linkage between tk and ras genes allowed the isolation of oncogene deletion revertants and of cell clones showing varying degrees of malignant phenotype. Southern and Northern experiments in concert with tumorigenicity assays show that the malignant transformation of these cells by mutant ras oncogenes is a gradual but reversible process that depends on the relative abundance of oncogene sequences and their corresponding transcripts. We also show that moderate amplification of a c-K-ras oncogene in these cells results in a clear increase in their tumorigenicity and that the mutant gene present in low copy numbers in cultured cells undergoes amplification in the corresponding in vivo induced tumors.

Documentos Relacionados

• Prevention of tumorigenesis of oncogene-transformed rat fibroblasts with DNA site inhibitors of poly(ADP ribose) polymerase.
• Prevention of tumorigenesis of oncogene-transformed rat fibroblasts with DNA site inhibitors of poly(ADP ribose) polymerase
• Defective HLA class II expression in a regulatory mutant is partially complemented by activated ras oncogenes.
• Differentiation of F9 embryonal carcinoma cells induced by the c-jun and activated c-Ha-ras oncogenes.
• Three human transforming genes are related to the viral ras oncogenes.