STEPWISE IMMORTALIZATION AND TRANSFORMATION OF ADULT HUMAN PROSTATE EPITHELIAL-CELLS BY A COMBINATION OF HPV-18 AND V-KI-RAS

Recent investigations have shown the presence of ras gene mutations an d human papillomavirus (HPV) DNA in prostate carcinomas. In the presen t study, secondary adult human prostatic epithelial cells, upon transf ection with a plasmid containing the entire HPV-18 genome, acquired an indefinite life-span in culture but did not undergo malignant convers ion. Subsequent infection of these immortalized cells with the Kirsten murine sarcoma virus, which contains an activated Ki-ras oncogene, in duced morphological transformation that led to the acquisition of neop lastic properties. These findings demonstrate the malignant transforma tion of adult human prostate epithelial cells in culture by a combinat ion of viral oncogenes and the successive roles of HPV infection and K i-ras activation in a multistep process responsible for prostate carci nogenesis.