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首页> 外文期刊>Journal of Cellular Physiology >Insulin-like growth factors modulate the growth inhibitory effects of retinoic acid on MCF-7 breast cancer cells.
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Insulin-like growth factors modulate the growth inhibitory effects of retinoic acid on MCF-7 breast cancer cells.

机译：胰岛素样生长因子调节的增长MCF-7视黄酸抑制的影响乳腺癌细胞。

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摘要

Retinoids are currently being tested for the treatment and prevention of several human cancers, including breast cancer. However, the anti-cancer and growth inhibitory mechanisms of retinoids are not well understood. All-trans retinoic acid (RA) inhibits the growth of the estrogen receptor-positive (ER+) breast cancer cell line, MCF-7, in a reversible and dose-dependent manner. In contrast, insulin-like growth factors (IGF-I, IGF-II) and insulin are potent stimulators of the proliferation of MCF-7 and several other breast cancer cell lines. Pharmacologic doses of RA (> or = 10(-6) M) completely inhibit IGF-I-stimulated MCF-7 cell growth. Published data suggest that the growth inhibitory action of RA on IGF-stimulated cell growth is linear and dose-dependent, similar to RA inhibition of unstimulated or estradiol-stimulated MCF-7 cell growth. Surprisingly, we have found that IGF-I or insulin-stimulated cell growth is increased to a maximum of 132% and 127%, respectively, by cotreatment with 10(-7) M RA, and that 10(-9) - 10(-7) M RA increase cell proliferation compared to IGF-I or insulin alone. MCF-7 cells that stably overexpress IGF-II are also resistant to the growth inhibitory effects of 10(-9) - 10(-7) M RA. Treatment with the IGF-I receptor blocking antibody, alpha IR-3, restores RA-induced growth inhibition of IGF-I-treated or IGF-II-overexpressing MCF-7 cells, indicating that the IGF-I receptor is mediating these effects. IGFs cannot reverse all RA effects since the altered cell culture morphology of RA-treated cells is similar in growth-inhibited cultures and in IGF-II expressing clones that are resistant to RA-induced growth inhibition. These results indicate that RA action on MCF-7 cells is biphasic in the presence of IGF-I or insulin with 10(-9) - 10(-7) M RA enhancing cell proliferation and > or = 10(-6) M RA causing growth inhibition. As IGF-I and IGF-II ligands are frequently detectable in breast tumor tissues, their potential for modulation of RA effects should be considered when evaluating retinoids for use in in vivo experimental studies and for clinical purposes. Additionally, the therapeutic use of inhibitors of IGF action in combination with RA is suggested by these studies.
机译：类维生素a目前正在进行的测试几个人的治疗和预防癌症,包括乳腺癌。抗癌和生长抑制机理类维生素a是不清楚。维甲酸(RA)抑制的增长雌激素受体阳性乳腺癌(ER +)细胞系,MCF-7可逆剂量依赖性的方式。生长因子(IGF-I IGF-II)和胰岛素MCF-7扩散的有力刺激器和其他几个乳腺癌细胞系。药物剂量的RA (> = 10 (6) M)完全抑制IGF-I-stimulated MCF-7细胞增长。RA IGF-stimulated细胞的抑制作用增长是线性的,存在剂量依赖的相关性,类似如果或RA抑制estradiol-stimulated MCF-7细胞生长。令人惊讶的是,我们发现IGF-I或刺激细胞生长是一个提高最大的132%和127%,分别cotreatment 10 (7) M RA, 10 (9) -10 (7) M RA相比增加细胞增殖IGF-I或胰岛素。稳定过表达IGF-II也抵抗10的生长抑制作用(9)- 10 (7)M类风湿性关节炎。抗体,αIR-3,恢复RA-induced增长抑制IGF-I-treated或IGF-II-overexpressing MCF-7细胞,指示IGF-I受体是调节效果。RA-treated的细胞培养形态学改变细胞在growth-inhibited文化和相似在抵抗IGF-II表达克隆RA-induced抑制增长。表明RA行动MCF-7细胞两相的IGF-I或胰岛素的存在10(9) - 10(7)米RA增强细胞增殖和> = 10 (6)M RA造成抑制增长。经常IGF-I和IGF-II配体可检测乳腺肿瘤组织中,他们的可能应该是RA的调制效果考虑当评估类维生素a的使用体内实验研究和临床目的。抑制剂结合RA IGF的行动由这些研究建议。

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