Effects of endogenous insulin-like growth factor binding protein-3 on cell cycle regulation in breast cancer cells.

Abstract

High tissue insulin-like growth factor binding protein-3 (IGFBP-3) expression in breast cancers is associated in some studies with rapid growth and poor outcome. This study examined the effects of endogenous IGFBP-3 in Hs578T breast cancer cells, which are IGF-unresponsive and grow aggressively despite relatively high IGFBP-3 expression. IGFBP-3 downregulation using siRNA was associated with increases in DNA synthesis, the percentage of cells in S phase and viable cell numbers, accompanied by increases in cyclins A and D1, a decrease in p27 expression, and increased phosphorylation of retinoblastoma (Rb) on Ser795. Downregulation of IGFBP-3 inhibited extracellular signal-regulated kinase (ERK) activation and cell migration in a monolayer wound healing assay. These results indicate that endogenous IGFBP-3 is anti-proliferative and pro-migratory in Hs578T cells and that these effects are IGF-independent. Poor outcome in breast tumours expressing high levels of IGFBP-3 may be due to the effects of IGFBP-3 on cell migration rather than cell growth.

• Authors: Michelle K O'Han, Robert C Baxter, Lynette J Schedlich
• Journal: Growth factors (Chur, Switzerland) (Growth Factors) Vol. 27 Issue 6 Pg. 394-408 (Dec 2009) ISSN: 1029-2292 [Electronic] England
• PMID: 19919528 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin-Like Growth Factor Binding Protein 3

Topics

• Breast Neoplasms (metabolism, pathology)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Female
• Humans
• Insulin-Like Growth Factor Binding Protein 3 (genetics, metabolism, pharmacology)
• RNA Interference