The protein kinase C activator, phorbol ester, elicits disparate functional responses in androgen-sensitive and androgen-independent human prostatic cancer cells

Biochem Biophys Res Commun. 1998 Mar 6;244(1):167-71. doi: 10.1006/bbrc.1998.8238.


The protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA) activated cell death in androgen-sensitive LNCaP cells but not in androgen-independent DU-145 or PC-3 cells, whose growth was significantly decreased by PKC inhibitors staurosporine and H7. All cell lines had similar levels of total PKC activities which, however, differed on their dependency on Ca2+ ions and lipid and were regulated differently by TPA. Furthermore, expression of the immediate early genes c-fos and c-jun was up-regulated by TPA only in LNCaP and DU-145 cells, whereas PC-3 cells failed to express c-fos mRNA. The regulation of the c-myc mRNA by TPA correlated inversely with activation of cell death being down-regulated in LNCaP cells, and slightly increased in the androgen-independent cell lines. These results suggest that the PKC signal transduction pathway functions differently in androgen-sensitive and insensitive prostatic cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / physiology*
  • Cell Division / drug effects
  • Cell Division / genetics
  • Enzyme Activation / drug effects
  • Epidermal Growth Factor / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genes, Immediate-Early / drug effects
  • Genes, fos / drug effects
  • Genes, jun / drug effects
  • Genes, myc / drug effects
  • Humans
  • Male
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Tumor Cells, Cultured


  • Androgens
  • Epidermal Growth Factor
  • Protein Kinase C
  • Tetradecanoylphorbol Acetate