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

Vivian Hwa, Youngman Oh, Ronald (Ron) Rosenfeld

Research output: Contribution to journalArticle

44 Citations (Scopus)

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 androgen-insensitive. 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.

Original languageEnglish (US)
Pages (from-to)235-242
Number of pages8
JournalEndocrine
Volume6
Issue number3
StatePublished - 1997

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Insulin-Like Growth Factor Binding Protein 5
Insulin-Like Growth Factor Binding Protein 3
Transforming Growth Factors
Tretinoin
Insulin-Like Growth Factor Binding Proteins
Prostate
Adenocarcinoma
Cell Line
Somatomedins
Messenger RNA
Proteins
Growth
Cell Proliferation
Androgens
Down-Regulation
Epithelial Cells
Neoplasms

Keywords

  • IGFBP-3
  • IGFBP-5
  • Prostate
  • Retinoic acid
  • TGF-β

ASJC Scopus subject areas

  • Endocrinology

Cite this

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. / Hwa, Vivian; Oh, Youngman; Rosenfeld, Ronald (Ron).

In: Endocrine, Vol. 6, No. 3, 1997, p. 235-242.

Research output: Contribution to journalArticle

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