||Introduction of a Ha-ras Oncogene into Rat Liver Epithelial Cells and Parenchymal Hepatocytes Confers Resistance to the Growth Inhibitory Effects of TGF-Beta.
Houck, K. A. ;
Michalopoulos, G. K. ;
Strom, S. C. ;
||Duke Univ. Medical Center, Durham, NC. Dept. of Pathology. ;Virginia Commonwealth Univ., Richmond.;Health Effects Research Lab., Research Triangle Park, NC.
Deoxyribonucleic acids ;
Transforming growth factors ;
Ras genes ;
||Most EPA libraries have a fiche copy filed under the call number shown. Check with individual libraries about paper copy.
Growth of rat liver epithelial cells (RLEC) and primary cultures of parenchymal hepatocytes is potently inhibited by TGF-Beta. Transfection of a mutated Ha-ras oncogene, but not a human c-myc oncogene, into RLEC resulted in cell lines resistant to growth inhibition by TGF-Beta under anchorage-dependent conditions. Infection of primary rat hepatocyte cultures with v-Ha-ras yielded a cell line likewise insensitive to inhibition by TGF-Beta. Binding of (125I)TGF-Beta to Ha-ras-transfected RLEC was reduced relative to control or c-myc-transfected cells. These data suggest that activation of a Ha-ras oncogene in epithelial cells may result in escape from negative growth control and hence be a critical step during carcinogenesis. (Copyright (c) 1989 The MacMillan Press Ltd.)