Insulin-like growth factor receptor expression and function in human breast cancer.
Insulin-like growth factor receptor expression and function in human breast cancer.
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发表时间：
1990
期刊：
影响因子：
11.2
通讯作者：
Kevin J. Cullen;Douglas Yee;William S. Sly;James F. Perdue;Brian Hampton;Marc E. Lippman;N. Rosen
中科院分区：
文献类型：
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作者：
Kevin J. Cullen;Douglas Yee;William S. Sly;James F. Perdue;Brian Hampton;Marc E. Lippman;N. Rosen
胰岛素样生长因子IGF-I和IGF-II是几种培养的乳腺肿瘤细胞系的有效有丝分裂原。此外，IGF-I和IGF-II mRNA在大多数乳腺肿瘤标本中很容易检测到，而我们研究的乳腺癌上皮细胞系均不表达真正的IGF-I mRNA，也很少有细胞系表达IGF-II mRNA。尽管已经描述了胰岛素、IGF-I和IGF-II的受体，但是在胰岛素/胰岛素样生长因子家族中的各种受体和配体之间存在显著的交叉反应性，并且不清楚哪种受体或哪种受体负责该系统中这些生长因子的生物学效应。使用RNA酶保护试验，我们检查了乳腺肿瘤标本和乳腺癌上皮细胞系的mRNA编码的I型和II型IGF受体以及胰岛素受体的表达。几乎所有检测的标本都表达了所有三种受体的mRNA。然后，我们在存在针对I型和II型受体的抗体的情况下检查了雌激素依赖性MCF-7细胞中IGF-I和II的促有丝分裂作用。阻断I型受体的单克隆抗体α IR-3消除了IGF-I和IGF-II的促有丝分裂作用。然而，它并不阻断胰岛素的促有丝分裂作用。我们得出结论，I型和II型IGF受体在乳腺癌中普遍表达，我们的MCF-7细胞实验表明IGF-I和IGF-II的促有丝分裂作用是通过I型IGF受体介导的。
The insulin-like growth factors IGF-I and IGF-II are potent mitogens for several breast tumor cell lines in culture. Additionally, both IGF-I and IGF-II mRNAs are easily detected in the majority of breast tumor specimens examined, while no breast cancer epithelial cell lines we have studied express authentic IGF-I mRNA, and few lines express IGF-II mRNA. Although receptors for insulin, IGF-I, and IGF-II have been described, there is significant cross-reactivity between the various receptors and ligands in the insulin/insulin-like growth factor family, and it is not clear which receptor or receptors are responsible for the biological effects of these growth factors in this system. Using an RNase protection assay, we examined breast tumor specimens and breast cancer epithelial cell lines for expression of mRNA encoding the type I and type II IGF receptors as well as the insulin receptor. Virtually all of the specimens examined expressed mRNA for all three receptors. We then examined estrogen-dependent MCF-7 cells for the mitogenic effects of IGF-I and II in the presence of antibodies to both the type I and type II receptors. alpha IR-3, a monoclonal antibody which blocks the type I receptor, abolished the mitogenic effects of both IGF-I and IGF-II. It did not, however, block the mitogenic effects of insulin. We conclude that type I and type II IGF receptors are ubiquitously expressed in breast cancer, and our experiments with MCF-7 cells suggest the mitogenic effects of both IGF-I and IGF-II are mediated via the type I IGF receptor.