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

The relationship between oestrogen (E-2) and insulin-like growth factor-one (IGF-1) was examined in both tamoxifen-sensitive (MCF 7/5-21) and tamoxife n-resistant (MGF 7/5-23) subclones of the MCF 7 cell line. Both subclones w ere grown in defined, serum-free (SF) medium over a period of 7 days with t he addition of E-2 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) b y E-2. However, only the growth of MCF 7/5-23 cells was stimulated (266%) b y IGF-1. A combination of E-2 and IGF-1 significantly enhanced MCF 7/5-21 a nd 7/5-23 cell growth (581% and 695%, respectively). E-2-induced IGF-1 rece ptor (IGF-1R) levels (as measured by I-125-IGF-1: binding and Northern anal yses) in only MCF 7/5-23 cells. This effect was partially inhibited by tamo xifen. in medium containing serum, the growth of only the MCF 7/5-23 cells was significantly inhibited by the IGF-1R monoclonal antibody, alpha 1R-3. The detection of E-2-induced expression of IGF-2 using RT-PCR was demonstra ted in the MCF 7/5-23 cells. These experiments indicate that E-2 may sensit ize tamoxifen-resistant MCF 7/5-23 cells to the growth stimulatory actions of IGF-2 via upregulation of the IGF-1R and describes a cell-survival mecha nism that may manifest itself as tamoxifen resistance.