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

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 recapitula te the genetic composition or biological behavior of primary prostate tumor s. Cell lines more appropriate for the study of human prostate primary tumo rs would be those derived from spontaneously immortalized cells; unfortunat ely, explanted prostate cells survive only short-term in culture, and rarel y immortalize spontaneously. Therefore, we examined whether cell lines deve loped through viral gene-mediated immortalization of human normal or primar y tumor prostate epithelium express aspects of the normal or malignant phen otypes, and could serve as appropriate models for normal or transformed hum an prostatic epithelium. METHODS. To accomplish these goals, we assessed the phenotypic expression o f cell cultures established through the immortalization of normal (1532N, 1 535N, 1542N, and PrEC-T) or malignant (1532T, 1535T, and 1542T) human prost ate epithelium with the E6 and E7 genes of HPV-16, or the large T antigen g ene 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 f orm colonies in soft. agar, or to form tumors in vivo, suggests that they m ay serve as valid, useful tools for the elucidation of prostate tumorigenes is. Moreover, the observation of structural alterations involving chromosom e 8, including gain of 8q in 3 of the 4 cell lines expressing aspects of th e malignant phenotype, implies that these cell lines accurately recapitulat e the genetic composition of primary prostate tumors. CONCLUSIONS. Taken together, these data suggest that cell Lines generated f rom immortalized normal or primary tumor epithelium may be useful for the e lucidation of early transforming events in the prostate. Prostate 44:164-17 1, 2000. (C) 2000 Wiley-Liss, Inc.