ANDROGEN-REPRESSED PHENOTYPE IN HUMAN PROSTATE-CANCER

An androgen-repressed human prostate cancer tell line, ARCaP, was esta blished and characterized. This cell line was derived from the ascites fluid of a patient with advanced metastatic disease, In contrast to t he behavior of androgen-dependent LNCaP and its androgen-independent C 4-2 subline, androgen and estrogen suppress the growth of ARCaP cells in a dose-dependent manner in vivo and in vitro, ARCaP is tumorigenic and highly metastatic. It metastasizes Ir to the lymph node. lung, pan creas, liver, kidney, and bone, and forms ascites fluid in athymic hos ts, ARCaP cells express low levels of androgen receptor mRNA and prost ate-specific antigen mRNA and protein. Immunohistochemical staining sh ows that ARCaP cells stain intensely for epidermal growth factor recep tor, c-erb B2/neu, and c-erb, B3. Staining is negative for chromograni n A and positive fur bombesin, serotonin, neuron-specific enolase, and the C-met protooncogene (a hepatic growth factor/scatter factor recep tor). ARCaP cells also secrete high levels of gelatinase A and B and s ome stromelysin, which suggests that this cell line may contain marker s representing invasive adenocarcinoma with selective neuronendocrine phenotypes. Along with its repression of growth, androgen is also foun d to repress the expression of prostate-specific antigen in ARCaP cell s as detected by a prostate-specific antigen promoter-beta-galactosida se reporter assay. Our results suggest that the androgen-repressed sta te may be central to prostate cancer progression and that advanced pro state cancer can progress from an androgen-independent to an androgen- repressed state.