Differential regulation of IGFBP-3 by the androgen receptor in the lineage-related androgen-dependent LNCaP and androgen-independent C4-2 prostate cancer models

Prostate. 2006 Jun 15;66(9):971-86. doi: 10.1002/pros.20420.

Abstract

Background: Despite evidence implicating insulin-like growth factor binding protein-3 (IGFBP-3) as a growth inhibitor of prostate cancer (CaP), little is known about changes in its regulation and function during progression to androgen independence.

Methods: The expression levels of IGFBP-3 were determined by cDNA microarray analysis and tissue microarrays (TMAs) after androgen ablations. LNCaP (LN-BP3) and C4-2 (C4-2-BP3) sublines were used to compare the apoptotic effects of IGFBP-3 in LNCaP (androgen-dependent) and C4-2 (androgen-independent) cells.

Results: After androgen deprivation, IGFBP-3 mRNA levels increased more in C4-2 compared to LNCaP cells. Androgens suppressed IGFBP-3 levels in a dose-dependent manner in LNCaP and C4-2 cell. IGFBP-3 expression was increased after NHT in human CaP tissues. Apoptotic rates increased in LN-BP3, but not C4-2-BP3 cells, following doxycycline-mediated IGFBP-3 induction.

Conclusions: C4-2 cell survival in an androgen-depleted environment may be facilitated through differential resistance to the apoptotic effects elicited by IGFBP-3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / pharmacology
  • Androgens / physiology*
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Cell Line, Tumor
  • Cell Lineage
  • Cell Survival
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Doxycycline / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / physiology*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / genetics*
  • Insulin-Like Growth Factor Binding Protein 3 / physiology
  • Male
  • Neoplasms, Hormone-Dependent / chemistry
  • Neoplasms, Hormone-Dependent / genetics
  • Neoplasms, Hormone-Dependent / pathology
  • Oligonucleotide Array Sequence Analysis
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Receptors, Androgen / physiology*

Substances

  • Androgens
  • Insulin-Like Growth Factor Binding Protein 3
  • RNA, Messenger
  • Receptors, Androgen
  • Doxycycline