Role of insulin-like growth factor binding proteins in 1alpha,25-dihydroxyvitamin D(3)-induced growth inhibition of human prostate cancer cells.

Abstract

BACKGROUND:

The mechanisms underlying 1alpha,25-dihydroxyvitamin D(3) (1,25D)-induced growth inhibition of human prostate cancer cells have not been fully elucidated. To determine whether alterations in the insulin-like growth factor (IGF) signaling axis are associated with 1,25D-induced growth inhibition, we examined the ability of 1,25D to regulate expression of IGF binding proteins (IGFBPs) in human prostate cancer cell lines.

METHODS:

Northern and Western blot analyses were used to detect 1,25D-induced alterations in IGFBP expression. Additional in vitro studies were performed to determine the role of IGFBP-3 in 1,25D-induced growth inhibition.

RESULTS:

1,25D decreased mRNA levels of the growth stimulatory IGFBP-2 and induced IGFBP-3 mRNA in LNCaP and C4-2 cells. 1,25D treatment also increased secreted IGFBP-3 protein levels in prostate cancer cell lines sensitive to 1,25D growth inhibition but had little effect on IGFBP-3 expression in 1,25D-resistant DU145 cells. However, recombinant IGFBP-3 had only a minor effect on LNCaP cell growth in the presence of serum. Furthermore, siRNA duplexes that reduced IGFBP-3 expression did not alter 1,25D growth inhibition in either LNCaP or PC-3 cell lines grown in serum-containing media.

CONCLUSIONS:

Our studies indicate 1,25D-induced up-regulation of IGFBP-3 is not required for the growth inhibitory effects of 1,25D in prostate cancer cells grown in serum-containing media.

• Authors: Lamonica V Stewart, Nancy L Weigel
• Journal: The Prostate (Prostate) Vol. 64 Issue 1 Pg. 9-19 (Jun 15 2005) ISSN: 0270-4137 [Print] United States
• PMID: 15651061 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Androgens
• Blood Proteins
• Calcium Channel Agonists
• Insulin-Like Growth Factor Binding Protein 2
• Insulin-Like Growth Factor Binding Protein 3
• RNA, Messenger
• Calcitriol

Topics

• Androgens (pharmacology)
• Blood Proteins (pharmacology)
• Calcitriol (pharmacology)
• Calcium Channel Agonists (pharmacology)
• Cell Division (drug effects)
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Insulin-Like Growth Factor Binding Protein 2 (genetics, metabolism)
• Insulin-Like Growth Factor Binding Protein 3 (genetics, metabolism)
• Male
• Prostatic Neoplasms (drug therapy, pathology, physiopathology)
• RNA, Messenger (analysis)
• Up-Regulation