Molecular mechanisms of androgen-independent growth of human prostate cancer LNCaP-AI cells

Endocrinology. 1999 Nov;140(11):5054-9. doi: 10.1210/endo.140.11.7086.


The goal of this study is to investigate the molecular mechanisms of androgen-independent growth in prostate cancer. We have established an androgen-independent prostatic carcinoma LNCaP-AI (defined as a LNCaP cell line that is capable of growing in charcoal-stripped serum) from the androgen-dependent LNCaP-FGC cells. In contrast to the androgen-independent PC-3 human prostate cancer cells, LNCaP-AI cells still express a similar level of androgen receptor as their parental cells and are sensitive to androgen stimulation. Compared with the parental LNCaP-FGC cells, LNCaP-AI cells are more resistant to apoptosis induced by 12-O-tetradecanoylphorbol-13-acetate and express a much higher level of antiapoptotic gene bcl-2 and cyclin-dependent kinase inhibitor p21, which may confer an enhanced antiapoptosis phenotype. On the other hand, expression of cyclin-dependent kinase inhibitor p16 is significantly reduced in the LNCaP-AI cells, implying the release of an inhibitory effect of p16 on cell cycle progression. Taken together, our results suggest that multiple factors contribute to the development of androgen-independent growth of prostatic carcinoma cells, including enhancement of cell antiapoptosis function, release of cell cycle inhibition, and stimulation of cell proliferation by alternative signaling pathways.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androgens / pharmacology*
  • Apoptosis / genetics
  • Cell Division / drug effects*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclins / genetics
  • DNA Fragmentation
  • Enzyme Inhibitors
  • Gene Expression
  • Humans
  • Male
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Receptors, Androgen / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Cells, Cultured


  • Androgens
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Androgen
  • Cyclin-Dependent Kinases
  • Tetradecanoylphorbol Acetate