Androgens decrease and retinoids increase the expression of insulin-like growth factor-binding protein-3 in LNcaP...

Area of Science:

• Endocrinology
• Molecular Biology
• Cancer Research

Background:

• Circulating insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) are linked to prostate cancer.
• Modulation of IGFBP-3 by retinoids may impact prostate tumor cell growth.

Purpose of the Study:

• To investigate the influence of androgens, retinoids, deltanoids, and thyroid hormone on IGFBP production in LNCaP prostate cancer cells.
• To determine if these changes in IGFBP production affect tumor cell growth.

Main Methods:

• LNCaP cells were treated with various agonists: R1881 (androgen), all-trans- and 9-cis-retinoic acid (retinoids), VD3 (deltanoid), and T3 (thyroid hormone).
• IGFBP expression was analyzed using Northern blot, Western ligand blotting, and radioimmunoassay.
• Cell growth was monitored under serum-free conditions.

Main Results:

• R1881 increased IGFBP-2 mRNA, an effect neutralized by atRA and VD3, but this was not observed at the protein level.
• R1881 decreased and atRA increased IGFBP-3 mRNA and protein levels.
• Retinoid effects on IGFBP-3 required high concentrations that also inhibited growth; R1881 decreased IGFBP-3 at both growth-promoting and inhibitory concentrations.
• No growth-modulating effect of IGFBP-3 was observed.

Conclusions:

• Nuclear receptor agonists influence IGFBP-3 secretion by LNCaP cells.
• The functional significance of these observed changes in IGFBP-3 secretion remains to be elucidated.