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Insulin-like growth factor binding protein-3 and-5 are regulated by transforming growth factor-β and retinoic acid in the human prostate adenocarcinoma cell line PC-3

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Abstract

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 androgeninsensitive. Both transforming growth factor-β (TGF-β) 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 β-2 (TGF-β2) (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-β, IGFBP-3, and IGFBP-5 protein concentrations were 14- and 9-fold, respectively, over that of controls. Cells treated with Ra (0–1 μM) also showed a time- and dose-dependent increase in IGFBP-3 protein and mRNA levels. However, in contrast to TGF-β2, high concentrations of RA (1 μM) 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-β 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.

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Authors and Affiliations

  1. Department of Pediatrics, NRC 5, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, 97201, Portland, OR

    Vivian Hwa, Youngman Oh & Ron G. Rosenfeld

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  1. Vivian Hwa
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  2. Youngman Oh
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  3. Ron G. Rosenfeld
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Hwa, V., Oh, Y. & Rosenfeld, R.G. Insulin-like growth factor binding protein-3 and-5 are regulated by transforming growth factor-β and retinoic acid in the human prostate adenocarcinoma cell line PC-3. Endocr 6, 235–242 (1997). https://doi.org/10.1007/BF02820498

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