Biochemicaland MorphologicalCharacterizationof ClonalAXC Rat ProstateCancerCells1

We used three heterogeneous parental cultures of LSC-AXC rat prostate cancer cells: LSC-AXC-C/0, cells maintained on culture medium; LSC-AXC-D/0, cells maintained on culture me dium containing 10~7 M 5<*-dihydrotestosterone; and LSC-AXCT/0, cells maintained on culture medium containing 10~7 M tes tosterone, to isolate clonally derived cell lines. Eleven of 15 clonal cell lines were tumorigenic when inoculated into intact male AXC rats. Eight tumorigenic clonal cell lines were selected for further evaluation, and all were found to possess features characteristic of secretory epithelium, as judged by light and electron micros copy. All parental cell lines and the eight selected clonal cell lines contained cytoplasmic and nuclear androgen receptors. Total receptor content was 131 ±61 (S.D.), 43 ±32, and 274 ±96 fmol/100 /¿gof DMA, respectively, for C-, D-, and T-cells. The differences were significant (p < 0.05). Androgen receptor con tent of young mature or senescent AXC rat ventral prostate, respectively, is 518 ±58 and 266 ±40 fmol/100 u,g of DMA. Since chromosomal analysis established that LSC-AXC prostate cancer cells are hypotriploid, androgen receptor content per cell in Cand T-cells is indicated to be either greater than or equal to that of senescent AXC rat ventral prostate, the tissue in which the original adenocarcinoma arose. Parental and clonal cell lines contained 5«-reductase activity. There were significant differ ences (p < 0.05) in both total reducÃ-aseactivity and metabolite distribution. Consequently, the ¡ntracellularcontent of testoster one metabolites was cell line specific. All characterized cell lines contained a higher concentration (p < 0.05) of APase activity than did young mature or senescent AXC rat ventral prostate. In 6 of 11 cell lines, prostate-secretory APase concentration ex ceeded (p < 0.05) that of AXC rat ventral prostate. However, the relative content of secretory APase compared to total APase in carcinoma cells consistently was less (p < 0.05) than that of AXC rat ventral prostate. These studies document the establish ment of clonal AXC rat prostate adenocarcinoma cell lines which have retained important morphological and phenotypic markers characteristic of differentiated prostate epithelium. Since these cells are tumorigenic and represent a spectrum of retained differentiated phenotypic markers, they should be particularly useful for in vivo and in vitro studies of hormonal regulation of prostate cancer cell behavior.