Androgen-repressed phenotype in human prostate cancer

Hai Yen E. Zhau, Shi Ming Chang, Bao Qi Chen, Yunling Wang, Hongquan Zhang, Chinghai Kao, Qingxiang Amy Sang, Sen J. Pathak, Leland W.K. Chung

Research output: Contribution to journalArticlepeer-review

184 Scopus citations

Abstract

An androgen-repressed human prostate cancer cell line, ARCaP, was established and characterized. This cell line was derived from the ascites fluid of a patient with advanced metastatic disease. In contrast to the behavior of androgen-dependent LNCaP and its androgen-independent C4-2 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 to the lymph node, lung, pancreas, liver, kidney, and bone, and forms ascites fluid in athymic hosts. ARCaP cells express low levels of androgen receptor mRNA and prostate-specific antigen mRNA and protein. Immunohistochemical staining shows that ARCaP cells stain intensely for epidermal growth factor receptor, c-erb B2/neu, and c-erb B3. Staining is negative for chromogranin A and positive for bombesin, serotonin, neuron- specific enolase, and the c-met protooncogene (a hepatic growth factor/scatter factor receptor). ARCaP cells also secrete high levels of gelatinase A and B and some stromelysin, which suggests that this cell line may contain markers representing invasive adenocarcinoma with selective neuronendocrine phenotypes. Along with its repression of growth, androgen is also found to repress the expression of prostate-specific antigen in ARCaP cells as detected by a prostate-specific antigen promoter-β-galactosidase reporter assay. Our results suggest that the androgen-repressed state may be central to prostate cancer progression and that advanced prostate cancer can progress from an androgen-independent to an androgen-repressed state.

Original languageEnglish (US)
Pages (from-to)15152-15157
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number26
DOIs
StatePublished - Dec 24 1996

Keywords

  • androgen receptor
  • bone metastasis
  • gene expression
  • metalloproteinases
  • prostate-specific antigen

ASJC Scopus subject areas

  • General

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