Insulin-like growth factor binding protein-3 and -5 are regulated by transforming growth factor-beta and retinoic acid in the human prostate adenocarcinoma cell line PC-3.
The family of insulin-like growth factor binding proteins (IGFBPs) can affect cell proliferation by modulating the availability and bioactivity of insulin-like growth factors (IGFs), or by mechanisms independent of IGFs. To understand better the role(s) of IGFBPs in prostate growth and malignancy, we examined the regulation of IGFBPs in PC-3 cells, a human prostatic adenocarcinoma epithelial cell line that is androgen-insensitive. Both transforming growth factor-beta (TGF-beta) and retinoic acid (RA), known inhibitors of cellular proliferation, significantly changed the IGFBP profile in PC-3 cells. In cells that were treated with transforming growth factor beta-2 (TGF-beta 2) (0.5-10 ng/mL), IGFBP-3, and IGFBP-5 protein and mRNA increased in a time- and dose-dependent manner. At 10 ng/mL TGF-beta, IGFBP-3, and IGFBP-5 protein concentrations were 14- and 9-fold, respectively, over that of controls. Cells treated with RA (0-1 microM) also showed a time- and dose-dependent increase in IGFBP-3 protein and mRNA levels. However, in contrast to TGF-beta 2, high concentrations of RA (1 microM) negatively regulated IGFBP-5 expression, with IGFBP-5 mRNA levels downregulated to 20% of that of the control, and protein levels were decreased by 50%. Since both TGF-beta and RA increased IGFBP-3 expression and both are known to inhibit prostate cell growth, we speculate that the inhibition of growth is mediated, at least in part, by IGFBP-3.
Hwa
V
V
Department of Pediatrics, Oregon Health Sciences University, Portland, Portland 97201, USA.
Oh
Y
Y
Rosenfeld
R G
RG
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015152:Blotting, Northern; D015153:Blotting, Western; D016895:Culture Media, Serum-Free; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology* / Q000502:physiology; D014407:Tumor Cells, Cultured
D016895:Culture Media, Serum-Free; D018972:Insulin-Like Growth Factor Binding Protein 3; D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014212:Tretinoin