Immortalized and tumorigenic adult human prostatic epithelial cell lines: Characteristics and applications part 2. Tumorigenic cell lines

Abstract

This is Part 2 of a three-part review and deals with tumorigenic cell lines. Several immortalized and malignant adult human prostatic epithelial cell lines have been recently developed. The three most widely used carcinoma cell lines-DU-145, PC-3, and LNCaP-developed between 1977 and1980, have greatly contributed to our current 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 the 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. The nontumorigenic cell lines were discussed in Part 1 [1]. This review summarizes the characteristics of several currently available tumorigenic, adult human prostatic epithelial cell lines.

Dipeptidyl Peptidase Inhibits Malignant Phenotype of Prostate Cancer Cells by Blocking Basic Fibroblast Growth Factor Signaling Pathway

“…The HPV-18 transformed and immortalized RWPE-1 cells represent early stage of prostate cancer progression because these cells neither grow in agar nor form tumors when injected into nude mice. Although RWPE-1 cells express cytokeratins 8 and 18, which are characteristic of luminal prostatic epithelial cells, they also coexpress basal cell cytokeratins (37). The DU-145 cell lines is AR negative and poorly differentiated, whereas the LNCaP cell line that exhibit less aggressive phenotype has functional AR, grows less rapidly, and is less tumorigenic than the DU-145 cell line.…”

Expression of a Truncated Form of the c-Kit Tyrosine Kinase Receptor and Activation of Src Kinase in Human Prostatic Cancer

“…The observation that the more undifferentiated and aggressive PC3 cells do not express tr-Kit, nor the nuclear factors that bind tr-Kit promoter, might be explained by the fact that PC3 cells are not representative of either normal or transformed prostatic cells. 30 In conclusion, our study demonstrates that a truncated form of c-Kit, previously shown to activate Src-like kinases, 13,16 is frequently expressed in prostate cancer and that its expression correlates with Src activation and phosphorylation of its substrate Sam68. Thus, our work suggests that activation of this pathway might contribute to the transformation of prostate cells.…”

Diallyl trisulfide-induced G2–M phase cell cycle arrest in human prostate cancer cells is caused by reactive oxygen species-dependent destruction and hyperphosphorylation of Cdc25C

“…Both cell lines are positive for cytokeratin 8 and cytokeratin 18 and negative for desmin confirming their epithelial origin (Webber et al, 1997a;Mitchell et al, 2000). The PC-3 cell line lacks p53 whereas the DU145 cell line expresses mutant p53 (Webber et al, 1997b).…”