IMMORTALIZATION OF PRIMARY RAT EMBRYO CELLS BY HUMAN PAPILLOMAVIRUS TYPE-11 DNA IS ENHANCED UPON COTRANSFER OF RAS

Transfer of human papillomavirus type 11 (HPV11) DNA and a neo marker into primary rat embryo cells (REC) led to colony formation in G418-selective medium. About 20% of HPV11 clones were eventually established in culture but displayed low growth rates. Cotransfection of HPV11 DNA and an activated ras oncogene led to formation of both drug-resistant flat colonies and phenotypically transformed clones which grew efficiently when expanded in culture. A number of transformants reverted to a flat, "normal" morphology shortly after isolation. Nontransformed clones expressed only HPV11 genes, while those maintaining a transformed phenotype transcribed both ras and HPV11 genes efficiently and were highly tumorigenic. Expression of HPV11 thus seems, necessary for induction of colony formation, but efficient long-term growth seems to require at least the transient presence of ras. © 1990.