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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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)
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Chemical References |
- Insulin-Like Growth Factor Binding Protein 3
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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
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