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

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 cDN A 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.