A novel human cancer culture model for the study of prostate cancer

Research into molecular and genetic mechanisms underlying prostate carcinog enesis would be greatly advanced by in vitro models of prostate tumors repr esenting primary tumors. We have successfully established an immortalized h uman prostate epithelial (HPE) cell culture derived from a primary tumor wi th telomerase. The actively proliferating early passaged RC-58T cells were transduced through infection with a retrovirus vector expressing the human telomerase catalytic subunit (hTERT). A high level of telomerase was detect ed in RC-58T/hTERT cells but not RC-58T cells. RC-58T/hTERT cells are curre ntly growing well at passage 50, whereas RC-58T cells senesced at passage 7 . RC-58T/hTERT cells exhibit transformed morphology. More importantly, thes e immortalized cells showed anchorage-independent growth as they formed col onies in soft agar and grew above the agar laver. Expression of androgen-re gulated prostate specific gene NKX3.1 and epithelial specific cytokeratin 8 (CK8) but not prostate specific antigen (PSA) and androgen receptor was de tected in RC-58T/hTERT cells. Prostate stem cell antigen (PSCA) and p16 wer e also expressed in this cell line. RC-58T/hTERT cells showed growth inhibi tion when exposed to retinoic acid and transforming growth factor (TGF)-bet a1 known potent inhibitors of prostate epithelial cell growth. A number of chromosome alterations were observed including the loss of chromosomes Y, 3 p, 10p, 17p, 18q and the gain of chromosomes 16 and 20. These results demon strate that this primary tumor-derived HPE cell line retained its transform ed phenotypes and should allow studies to elucidate molecular and genetic a lterations involved in prostate cancer. This is the first documented case o f an established human prostate cancer cell line from a primary tumor of a prostate cancer patient with telomerase.