Insulin-like growth factor binding protein-3 expression is associated with growth stimulation of T47D human breast cancer cells: the role of altered epidermal growth factor signaling.

Abstract	IGF binding protein (IGFBP)-3 has antiproliferative and proapoptotic effects on the growth of human breast cancer cells in vitro. However, clinical studies suggest that high levels of IGFBP-3 in breast tumor tissue are associated with large, highly proliferative tumors. In this study, we examined the effects of stable transfection with human IGFBP-3 cDNA on the growth of T47D human breast cancer cells in vitro and in vivo. Expression of IGFBP-3 initially inhibited the growth of T47D in vitro but was associated with enhanced growth in vivo. Furthermore, IGFBP-3-expressing cells in vitro became growth stimulated at higher passages post transfection, suggesting breast cancer cells may switch their response to IGFBP-3 with increasing tumorigenicity. These stimulatory effects observed in IGFBP-3-expressing cells were associated with an enhanced responsiveness to the proliferative effects of epidermal growth factor (EGF). When EGF receptor (EGFR) kinase activity was blocked using PD153035, high passage IGFBP-3 transfectants were growth inhibited compared with controls treated with inhibitor. These findings suggest that the interaction between IGFBP-3 and the EGFR system is central to whether IGFBP-3 acts as a growth stimulator or inhibitor in breast cancer cells and that therapies targeting EGFR may have increased efficacy in breast tumors expressing high levels of IGFBP-3.
Authors	Alison J Butt, Janet L Martin, Kristie A Dickson, Fiona McDougall, Sue M Firth, Robert C Baxter
Journal	The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 89 Issue 4 Pg. 1950-6 (Apr 2004) ISSN: 0021-972X [Print] United States
PMID	15070968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Insulin-Like Growth Factor Binding Protein 3 Epidermal Growth Factor ErbB Receptors
Topics	Animals Breast Neoplasms (metabolism, pathology) Cell Division Cell Line, Tumor Epidermal Growth Factor (metabolism, pharmacology) ErbB Receptors (metabolism) Female Humans Insulin-Like Growth Factor Binding Protein 3 (metabolism) Mice Mice, Nude Signal Transduction Up-Regulation

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