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

Growth Factors
Michelle K O'HanLynette J Schedlich

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.

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May 2, 2012·Pathology Oncology Research : POR·A KulkarniB A Chandramouli
Oct 20, 2011·Biochemical and Biophysical Research Communications·Je Yeong KoJong Hoon Park
Sep 24, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lili BaoYiwen You

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