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

Research into molecular and genetic mechanisms underlying familial prostate cancer would be greatly advanced by in vitro models of prostate tumor cell s representing primary tumors. We have successfully established an immortal ized human prostate epithelial cell culture derived from primary tumors of familial prostate cancer patients with telomerase. The actively proliferati ng early-passaged 957E cells were transduced through infection with a retro virus expressing the human telomerase catalytic subunit, human telomerase r everse transcriptase (hTERT). A high level of telomerase activity was detec ted in 957E/hTERT cells, but not in 957E cells. 957E/hTERT cells are curren tly growing well at passage 40, whereas 957E cells senesced at passage 5. 9 57E/hTERT cells exhibit epithelial morphology. Expression of an androgen-re gulated prostate specific homeobox gene NKX3.1 and an epithelial cell-speci fic cytokeratin 8, but not prostate specific antigen or androgen receptor, was detected in 957E/hTERT cells. Prostatic stem cell antigen and p 16 were also expressed in this line. 957E/hTERT cells showed growth inhibition whe n exposed to retinoic acid and transforming growth factor beta1, potent inh ibitors of prostate epithelial cell growth. Chromosome analysis showed that the 957E/hTERT cell line (passage 10) was near diploid human male (XY), wi th most chromosome counts in the 44-46 range. However, there was random los s of chromosomes 8, 13, X, Y, and alteration in chromosome 4q. The late pas sage 957E/hTERT cell line (passage 32) was karyologically similar to the ea rly passage 957E/hTERT cell line (passage 10) and also had the same alterat ion of 4q observed in the early passage 957E/hTERT cell line (passage 10) a s well as a trisomy of chromosome 20. The well-characterized human cancer l ines derived from such patients will be useful for the identification and c haracterization of prostate cancer susceptibility genes. This is the first documented case of an established human prostate cancer cell line from prim ary tumor of a familial prostate cancer patient.