Re-expression of estrogen receptor alpha in estrogen receptor alpha-negative MCF-7 cells restores both estrogen and insulin-like growth factor-mediated signaling and growth.

摘要: Estrogen can increase insulin-like growth factor-I receptor (IGF-IR) and insulin substrate-1 (IRS-1) expression, two key components of IGF-I-mediated signaling. The result is sensitization breast cancer cells to IGF-I synergistic in the presence estrogen IGF-I. We hypothesized that loss alpha (ERalpha) would reduced IGF-mediated signaling growth. To test this hypothesis, we examined effects MCF-7 cell sublines have been selected for ERalpha (C4 C4-12 are ERalpha-negative) by long-term withdrawal. C4 had IGF-IR IRS-1 mRNA protein expression (compared with cells) was not inducible estrogen. Furthermore, showed failed show any response either or prove IGF estrogen-mediated a consequence ERalpha, re-expressed stable transfection HA-tagged ERalpha. Three independent ERalpha-HA clones expressed functional (a) down-regulated estrogen, (b) conferred estrogen-induction cyclin D1 (c) caused number S phase. All were completely blocked antiestrogens. Interestingly, did restore induction progesterone expression. However, ERalpha-positive now exhibited levels responded mitogenically both These data critical requirement signaling, our knowledge first report confers an ER-negative line.