Evidence for a novel mechanism of androgen resistance in the human prostate cancer cell line, PC-3

Steroids. 1995 Jan;60(1):180-6. doi: 10.1016/0039-128x(94)00031-7.


Progression to hormone-refractory disease is a common outcome of human prostate cancer. In this study, we have investigated the basis of androgen insensitivity in the human prostate cancer cell line, PC-3, which was derived from a bone metastasis of a hormone-refractory prostate cancer. PC-3 cells with virtually undetectable (PC-3AR-) or low (PC-3AR+) levels of androgen receptor (AR) RNA expression were examined. RNase protection assays demonstrated that the level of AR RNA in PC-3AR+ cells was similar to that in a normal androgen-responsive genital skin fibroblast cell strain. Quantitative immunocytochemical staining of AR in PC-3AR+ cells using antibodies directed against the amino and carboxyl termini of the receptor revealed staining in 30% of cells with either antibody. Furthermore, the level of AR staining in PC-3AR+ cells was higher than in the androgen-responsive breast cancer cell lines ZR-75-1, T47-D, and MCF-7. Despite the expression of AR RNA and protein, PC-3AR+ cell proliferation was unaffected by the presence of 0.1-10 nM mibolerone. Scatchard analysis demonstrated a complete absence of specific [3H]dihydrotestosterone ([3H]DHT) binding to PC-3AR+ cytosolic extracts, which could not be explained by structural alterations in the AR gene. The sizes of individual AR exons amplified from genomic DNA derived from PC-3AR+ cells were identical to those amplified from normal human cells. Furthermore, sequence analysis did not reveal a mutation in the DNA- or hormone-binding domains of the AR gene in PC-3AR+ cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / pharmacology*
  • Cell Division / drug effects
  • Drug Resistance
  • Humans
  • Immunohistochemistry
  • Male
  • Neoplasm Proteins / biosynthesis*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • RNA, Neoplasm / biosynthesis*
  • Radioligand Assay
  • Receptors, Androgen / genetics*
  • Tumor Cells, Cultured


  • Androgens
  • Neoplasm Proteins
  • RNA, Neoplasm
  • Receptors, Androgen