Hye. Zhau et al., ANDROGEN-REPRESSED PHENOTYPE IN HUMAN PROSTATE-CANCER, Proceedings of the National Academy of Sciences of the United Statesof America, 93(26), 1996, pp. 15152-15157
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.