Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells.
Insulin receptor substrates mediate distinct biological responses to insulin-like growth factor receptor activation in breast cancer cells.
复制标题
DOI：
10.1038/sj.bjc.6603354
复制
发表时间：
2006-11-06
影响因子：
8.8
通讯作者：
Yee, D.
中科院分区：
文献类型：
--
作者：
Byron, S. A.;Horwitz, K. B.;Richer, J. K.;Lange, C. A.;Zhang, X.;Yee, D.
关键词：
I型胰岛素样生长因子受体(IGF-IR)的激活调节恶性表型的几个方面，包括癌细胞的增殖和转移。IGF-IR下游接头蛋白的磷酸化可能会将IGF的作用偶联到特定的癌症表型。在这项研究中，我们试图确定胰岛素受体底物-1和-2(IRS-1和-2)是否在乳腺癌细胞中介导不同的生物学效应。T47D-YA乳腺癌细胞表达胰岛素受体底物-1和IRS-2，表达IRS-1和IRS-2，但保留功能性IGF-IR。在IRS-1和IRS-2表达缺失的情况下，IGF-IR的激活不能刺激T47D-YA细胞的增殖或运动。IRS-1的表达促进了IGF-I刺激的细胞增殖，但不影响细胞的运动能力。相反，IRS-2的表达增强了IGF-I刺激的运动能力，但不能刺激增殖。胰岛素样生长因子-IR的抑制剂α-IR-3不能影响胰岛素样生长因子刺激的表型，除非表达胰岛素样生长因子-1或-2。因此，IGF-IR单独不能调节重要的乳腺癌细胞表型。在这些细胞中，IRS蛋白是IGF-IR刺激行为的不同方面所必需的，并参与其调节。由于多个靶向IGF-IR的药物目前处于早期临床试验中，IRS的表达应被视为IGF-IR反应性的潜在生物标志物。
Activation of the type I insulin-like growth factor receptor (IGF-IR) regulates several aspects of the malignant phenotype, including cancer cell proliferation and metastasis. Phosphorylation of adaptor proteins downstream of IGF-IR may couple IGF action to specific cancer phenotypes. In this study, we sought to determine if insulin receptor substrate-1 and -2 (IRS-1 and -2) mediate distinct biological effects in breast cancer cells. Insulin receptor substrate-1 and IRS-2 were expressed in T47D-YA breast cancer cells, which lack IRS-1 and -2 expression, yet retain functional IGF-IR. In the absence of IRS-1 and -2 expression, IGF-IR activation was unable to stimulate proliferation or motility in T47D-YA cells. Expression of IRS-1 resulted in IGF-I-stimulated proliferation, but did not affect motility. In contrast, expression of IRS-2 enhanced IGF-I-stimulated motility, but did not stimulate proliferation. The αIR-3, an inhibitor of the IGF-IR, was unable to affect these IGF-stimulated phenotypes unless IRS-1 or -2 was expressed. Thus, IGF-IR alone is unable to regulate important breast cancer cell phenotypes. In these cells, IRS proteins are required for and mediate distinct aspects of IGF-IR-stimulated behaviour. As multiple agents targeting the IGF-IR are currently in early clinical trials, IRS expression should be considered as a potential biomarker for IGF-IR responsiveness.
登录
查看更多内容
影响因子：
11.4
作者：
KASTNER, P;KRUST, A;CHAMBON, P
通讯作者：
CHAMBON, P
影响因子：
5.6
作者：
FIGUEROA, JA;SHARMA, J;YEE, D
通讯作者：
YEE, D
影响因子：
8
作者：
Jackson, JG;Zhang, XH;Yee, D
通讯作者：
Yee, D
影响因子：
3.8
作者：
ARTEAGA, CL
通讯作者：
ARTEAGA, CL
影响因子：
1.4
作者：
Jackson, JG;Yee, D
通讯作者：
Yee, D