Insulin/IGF-1 modulation of the expression of two estrogen-induced genes in MCF-7 cells
Insulin/IGF-1 modulation of the expression of two estrogen-induced genes in MCF-7 cells
复制标题
DOI：
10.1016/0303-7207(96)03844-0
复制
发表时间：
1996-07-23
影响因子：
4.1
通讯作者：
Green, CD
中科院分区：
文献类型：
--
作者：
ElTanani, MKK;Green, CD
人类乳腺癌细胞系的雌激素反应经常被证明是由胰岛素促进的。我们研究了胰岛素的作用及其与雌二醇的相互作用，在调节雌激素诱导基因LIV-1和pS2的表达。这两种激素都会引起两种基因mRNA水平的增加，但作用机制不同。产生这种效果所需的胰岛素浓度表明，它是通过与IGF-1受体结合的能力起作用的。胰岛素和雌二醇都在转录水平上发挥作用。胰岛素的诱导依赖于持续的蛋白质合成，而雌二醇的诱导则不是。纯抗雌激素（ICI 164384）可阻止胰岛素和雌二醇的诱导作用，表明需要一种可激活的雌激素受体。胰岛素不通过雄激素受体刺激LIV-1的表达。这些结果表明，雌二醇和胰岛素都可以通过不同的机制刺激这些雌激素诱导基因的转录，这两种机制都涉及雌激素受体。
Estrogen responses of human breast cancer cell lines have frequently been shown to be promoted by insulin. We have examined the action of insulin, and its interaction with estradiol, in regulating the expression of the estrogen-induced genes, LIV-1 and pS2. Both hormones cause increases in mRNA levels of the two genes but do so by distinct mechanisms. The concentration of insulin required to produce this effect suggests that it is acting via its ability to bind to the IGF-1 receptor. Both insulin and estradiol exert their effects at the level of transcription. Induction by insulin is dependent upon continued protein synthesis whereas induction by estradiol is not. Induction by both insulin and estradiol is prevented by the pure antiestrogen, ICI 164384, indicating the requirement for an activatable estrogen receptor. Insulin does not stimulate LIV-1 expression via the androgen receptor. These results demonstrate that both estradiol and insulin can stimulate the transcription of these estrogen-inducible genes, by separate mechanisms both of which involve the estrogen receptor.