Immortalized and tumorigenic adult human prostatic epithelial cell lines: characteristics and applications. Part I. Cell markers and immortalized nontumorigenic cell lines.

Abstract

Several immortalized and malignant adult human prostatic epithelial cell lines have recently been developed. The three most widely used carcinoma cell lines, DU-145, PC-3, and LNCaP, developed between 1977 and 1980, have greatly contributed to our present understanding of prostate cancer. Before a cell line can be accepted as having prostatic epithelial origin, some basic characteristics must be established. Expression of specific cytokeratins, but absence of desmin and factor VIII, should be first determined to establish epithelial origin. Responsiveness to androgens and expression of androgen receptor and prostate specific antigen should be examined under stringent culture conditions to establish prostatic epithelial origin. Response to growth factors and expression of their receptors facilitates further characterization of cell behavior. Cell lines immortalized by human papillomaviruses (HPVs) are of special interest because HPVs are involved in a variety of anogenital cancers and may also play a role in prostate carcinogenesis. Malignant transformation of HPV-18 immortalized cells with the ras oncogene provides cell systems for investigating the multistep process of carcinogenesis. Each cell line has some unique characteristics, whether it arose directly from a carcinoma or resulted from immortalization with simian virus 40 (SV40) or HPV or was transformed in vitro by oncogenes. Comparisons of these characteristics should facilitate elucidation of the mechanisms involved in initiation, promotion, and progression of prostate cancer. These cell lines will further serve as useful models for investigating tumor progression, invasion, metastasis, new therapeutic strategies, drug resistance, and its reversal and chemoprevention. This review will be published in three parts and will summarize cell markers necessary for characterization, as well as the characteristics and some applications of the immortalized as well as malignant adult human prostatic epithelial cell lines. Part 1 deals with cell markers and the immortalized, nontumorigenic cell lines.