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. 1999 Feb;79(5-6):693–700. doi: 10.1038/sj.bjc.6690112

Altered expression of the IGF-1 receptor in a tamoxifen-resistant human breast cancer cell line

J P Parisot 1, X F Hu 1, M DeLuise 2, J R Zalcberg 1
PMCID: PMC2362670  PMID: 10070856

Abstract

The relationship between oestrogen (E2) and insulin-like growth factor-one (IGF-1) was examined in both tamoxifen-sensitive (MCF 7/5–21) and tamoxifen-resistant (MCF 7/5–23) subclones of the MCF 7 cell line. Both subclones were grown in defined, serum-free (SF) medium over a period of 7 days with the addition of E2 or IGF-1 or a combination of both agents. Growth of both MCF 7/5–21 and 7/5–23 cells was stimulated (245% and 350%, respectively) by E2. However, only the growth of MCF 7/5–23 cells was stimulated (266%) by IGF-1. A combination of E2 and IGF-1 significantly enhanced MCF 7/5–21 and 7/5–23 cell growth (581% and 695%, respectively). E2-induced IGF-1 receptor (IGF-1R) levels (as measured by 125 I-IGF-1 binding and Northern analyses) in only MCF 7/5–23 cells. This effect was partially inhibited by tamoxifen. In medium containing serum, the growth of only the MCF 7/5–23 cells was significantly inhibited by the IGF-1R monoclonal antibody, αIR-3. The detection of E2-induced expression of IGF-2 using RT-PCR was demonstrated in the MCF 7/5–23 cells. These experiments indicate that E2 may sensitize tamoxifen-resistant MCF 7/5–23 cells to the growth stimulatory actions of IGF-2 via up-regulation of the IGF-1R and describes a cell-survival mechanism that may manifest itself as tamoxifen resistance. © 1999 Cancer Research Campaign

Keywords: breast cancer, IGF-1R, oestrogen, tamoxifen resistance

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Selected References

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