IMMORTALIZED AND TUMORIGENIC ADULT HUMAN PROSTATIC EPITHELIAL-CELL LINES - CHARACTERISTICS AND APPLICATIONS .3. ONCOGENES, SUPPRESSOR GENES, AND APPLICATIONS

This is Part 3 of a three-part review. It deals with the possible role of oncogenes and suppressor genes in human prostate carcinoma as well applications of nontumorigenic and tumorigenic human prostate cell li nes described in Parts 1 and 2 [1,2]. Several immortalized and maligna nt adult human prostatic epithelial cell lines have recently been deve loped. The three most widely used carcinoma cell lines, DU-145, PC-3, and LNCaP, developed between 1977 and 1980, have greatly contributed t o our present understanding of prostate canter. Before a cell line can be accepted as having prostatic epithelial origin, some basic charact eristics must be established. Expression of specific cytokeratins but absence of desmin and factor VIII should be first determined to establ ish epithelial origin. Responsiveness to androgens and expression of a ndrogen receptor and prostate-specific antigen should be examined unde r stringent culture conditions to establish prostatic epithelial origi n. Response to growth factors and expression of their receptors facili tates further characterization of cell behavior. Cell lines immortaliz ed by human papillomaviruses (HPVs) are of special interest because HP Vs are involved in a variety of anogenital cancers and may also play a role in prostate carcinogenesis. Malignant transformation of HPV-18 i mmortalized cells with the ras oncogene provides cell systems for inve stigating the multistep process of carcinogenesis. Each cell line has some unique characteristics, whether it arose directly from a carcinom a or resulted from immortalization with simian virus 40 (SV40) or HPV, or was transformed in vitro by oncogenes. Comparisons of these charac teristics should facilitate elucidation of the mechanisms involved in initiation, promotion and progression of prostate cancer. These cell l ines will further serve as useful models for investigating tumor progr ession, invasion, metastasis, new therapeutic strategies, drug resista nce and its reversal and chemoprevention. This review summarizes some applications of the currently available immortalized, non-turmorigenic as well as the tumorigenic adult human prostatic epithelial cell line s. (C) 1997 Wiley-Liss, Inc.