The Cooperation between Viral ras Genes and Different Immortalizing Genes Induces the Transformation of Rat Thyroid Epithelial Cells

Abstract

Oncogenes of the ras family have been isolated from different human and experimental carcinomas by transfecting high molecular weight DNA onto NIH 3T3 fibroblasts. The activated ras genes differ from normal ones by point mutations in specific regions of the genes (1, 2) . This finding has allowed to establish new more sophisticated and more sensitive techniques to evidenciate point mutations of the ras genes in human tumors. In fact, using a combinations of techniques, including specific in vitro gene amplification by the polymerase chain reaction (PCR) and mutation detection by cleavage at single base mismatches by RNAase A in DNA:RNA and RNA:RNA heteroduplexes, it has been possible to evidentiate point mutations of the ras-Ki oncogene in 21 out of 22 human carcinomas of the exocrine pancreas and in the 40% of the human colorectal cancers (3, 4) . However, a problem that could be raised is whether or not these mutations in the ras genes are the unique events responsible for the carcinogenesis process. In fact, studies of chemical carcinogenesis, as well as epidemiological analysis of malignancies in humans (5, 6, 7), strongly suggest that the neoplastic transformation is a multistage process and the observation that two different oncogenes are required in concert for malignant conversion of nonestablished rat cells confirms this point of view (8, 9).