Document Detail


Effects of endogenous insulin-like growth factor binding protein-3 on cell cycle regulation in breast cancer cells.
MedLine Citation:
PMID:  19675966     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2009-8-12
Journal Detail:
Title:  Growth factors (Chur, Switzerland)     Volume:  -     ISSN:  1029-2292     ISO Abbreviation:  Growth Factors     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-8-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9000468     Medline TA:  Growth Factors     Country:  -    
Other Details:
Languages:  ENG     Pagination:  1     Citation Subset:  -    
Affiliation:
Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, Sydney, NSW, Australia.
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