Phenotypic characterization of immortalized normal and primary tumor-derived human prostate epithelial cell cultures

Abstract

BACKGROUND Cell lines can provide powerful model systems for the study of human tumorigenesis. However, the human prostate cancer cell lines studied most intensively by investigators (PC3, DU145, and LNCaP) were established from metastatic lesions, and it is unlikely that they accurately recapitulate the genetic composition or biological behavior of primary prostate tumors. Cell lines more appropriate for the study of human prostate primary tumors would be those derived from spontaneously immortalized cells; unfortunately, explanted prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we examined whether cell lines developed through viral gene-mediated immortalization of human normal or primary tumor prostate epithelium express aspects of the normal or malignant phenotypes, and could serve as appropriate models for normal or transformed human prostatic epithelium. METHODS To accomplish these goals, we assessed the phenotypic expression of cell cultures established through the immortalization of normal (1532N, 1535N, 1542N, and PrEC-T) or malignant (1532T, 1535T, and 1542T) human prostate epithelium with the E6 and E7 genes of HPV-16, or the large T antigen gene of SV40. RESULTS Examination of these cell lines for their proliferative rates and their abilities to grow with or without serum or androgen stimulation, to form colonies in soft agar, or to form tumors in vivo, suggests that they may serve as valid, useful tools for the elucidation of prostate tumorigenesis. Moreover, the observation of structural alterations involving chromosome 8, including gain of 8q in 3 of the 4 cell lines expressing aspects of the malignant phenotype, implies that these cell lines accurately recapitulate the genetic composition of primary prostate tumors. CONCLUSIONS Taken together, these data suggest that cell lines generated from immortalized normal or primary tumor epithelium may be useful for the elucidation of early transforming events in the prostate. Prostate 44:164–171, 2000. © 2000 Wiley-Liss, Inc.