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Lipofection-mediated Immortalization of Human Prostatic Epithelial Cells of Normal and Malignant Origin Using Human Papillomavirus Type 18 DNA¹

Department of Urology, Stanford University School of Medicine, Stanford, California 94305 [S. T. W., D. M. P.], and Departments of Urology [P. C. W., J. J. K.] and Virology [H. G. M. N.], Erasmus University of Rotterdam, 3000 DR Rotterdam, The Netherlands

Human papillomavirus (HPV) type 18 DNA was introduced into epithelial cell strains derived from normal and cancer tissues of human prostatectomy specimens by the lipofection transfection method. Two cell lines were established: PZ-HPV-7 (transfected normal cell) and CA-HPV-10 (transfected cancer-derived cell). These lines have been maintained for over 100 passages. Incorporation of HPV type 18 DNA was confirmed by polymerase chain reaction. Immunocytochemical analysis showed expression of keratins 5 and 8, similar to the cells of origin, and the early region 6 oncoprotein of HPV. PZ-HPV-7, derived from normal diploid cells, had a modal chromosome number of 46 in early passages but became tetraploid later. CA-HPV-10 cells were aneuploid, and some retained the double minute chromosomes that were noted in the cancer-derived cells of origin. The cell lines showed a typical transformed morphology and were nontumorigenic in nude mice. We conclude that human prostatic epithelial cells derived from both normal and cancer tissues have been successfully transformed to immortality with HPV type 18 DNA. The establishment of these cell lines provides an opportunity for further development of an in vitro model of carcinogenesis for prostate cancer.

¹ Supported by the Lucas Foundation, the European Urological Scholarship Foundation, the Fulbright Program, and the De Drie Lichten Foundation.

² To whom requests for reprints should be addressed.

Received 7/15/94. Accepted 8/31/94.

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