Malignant transformation in a nontumorigenic human prostatic epithelial cell line

The human prostatic epithelial cell line BPH-1 is normally nontumorigenic i n nude mice. The present report demonstrates that this cell line can be per manently transformed by its microenvironment to become tumorigenic. The est ablishment of a series of tumorigenic sublines based on this parental cell line is described. BPH-1 cells were induced to form tumors either by recomb ination with human prostatic carcinoma-associated fibroblasts (CAFs) or by exposure to carcinogenic doses of testosterone and estradiol (T+E2) after r ecombination with rat urogenital sinus mesenchyme. Epithelial cells isolate d from these tumors were established as cell strains in culture. When regra fted to nude mouse hosts epithelial cells isolated from CAF- or T+E2-induce d tumors were found to be consistently tumorigenic even in the absence of C AF or T+E2. The T+E2-induced cell strains have been designated BPH1(TETD)-A and -B and the CAF-induced strains are designated BPH1(CAFTD)-01 through - 08. In vitro, the cells had an epithelial morphology with a less well-defin ed cobblestone pattern than the parental line. They express SV40 large T an tigen, confirming their derivation from the parental BPH-l line. The BPH1(C AFTD) strains formed colonies in soft agar, whereas the parental BPH-1 cell s and the BPH1(TETD) sublines did not. There was no immunocytochemically de tectable expression of androgen (AR), alpha -estrogen (ER alpha), or proges terone (PR) receptors by the parental BPH-1 cell line or by any of the tumo r-derived cell strains. The cells uniformly coexpressed both basal and lumi nal cell-type cytokeratins and the basal cell marker p63. hen grafted benea th the renal capsule of athymic mouse hosts, all of the tumor-derived cell strains consistently formed tumors. These were predominantly poorly or mode rately differentiated squamous or adenosquamous tumors, similar in organiza tion to the primary tumors from which the cell strains were derived. The ce ll strains continued to express both basal- and luminal-type cytokeratins i n vivo. Some of the cell strains also coexpressed vimentin. E-cadherin expr ession was absent from many of the cells, although patches of cells express ing this marker were seen. The cells continued to express SV40T antigen. Th ese cell strains, which are all derived from a common nontumorigenic progen itor, represent a useful resource for examining genetic and phenotypic chan ges during carcinogenesis.