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

Alison J. Butt*, Janet L. Martin, Kristie A. Dickson, Fiona McDougall, Sue M. Firth, Robert C. Baxter

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1950-1956
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Volume89
Issue number4
DOIs
Publication statusPublished - 1 Apr 2004
Externally publishedYes

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