IRS-1 expression and activation are not sufficient to activate downstream pathways and enable IGF-I growth response in estrogen receptor negative breast cancer cells
IRS-1 expression and activation are not sufficient to activate downstream pathways and enable IGF-I growth response in estrogen receptor negative breast cancer cells
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DOI：
10.1054/ghir.1999.0113
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发表时间：
1999-10-01
影响因子：
1.4
通讯作者：
Yee, D
中科院分区：
文献类型：
--
作者：
Jackson, JG;Yee, D
IGF-反应性乳腺癌细胞在 IGF-1 处理后激活胰岛素受体底物 (IRS)-1。为了确定IRS-I表达是否足以产生IGF反应性，用IRS-1转染两种IGF-1无反应性乳腺癌细胞系（MDA-MB-435A和MDA-MB-468）。虽然 IGF-I 在两种转染的细胞系中引起 IRS-I 的酪氨酸磷酸化，但没有观察到 MAP 激酶活性增加。 IGF-1处理435A IRS-1转染细胞导致与IRS-1相关的P13激酶活性轻微增加，而IRS-2/P13激酶大大降低。在MDA-MB-468 IRS-I转染的细胞中，与亲本细胞相比，IGF-I导致IRS-1相关的P13激酶活性增加，但其水平远低于在IGF反应性MCF-7细胞中观察到的水平。转染的细胞在单层生长中对 IGF-1 也没有反应。因此，单独的IRS-1表达和激活不足以介导乳腺癌细胞中对IGF-1的增殖反应，并且下游信号通路的最大激活可能也必须发生。 (C) 1999 哈考特出版有限公司。
IGF-responsive breast cancer cells activate insulin receptor substrate (IRS)-1 after IGF-1 treatment. To determine if IRS-I expression was sufficient to enable IGF-responsiveness, two IGF-1 unresponsive breast cancer cell lines (MDA-MB-435A and MDA-MB-468) were transfected with IRS-1. While IGF-I caused tyrosine phosphorylation of IRS-I in both transfected cell lines, increased MAP kinase activity was not seen. IGF-1 treatment of 435A IRS-1 transfected cells resulted in minimal increased P13 kinase activity associated with IRS-l,while IRS-2/P13 kinase was greatly reduced. in MDA-MB-468 IRS-I transfected cells, IGF-I caused increased IRS-1 associated P13 kinase activity compared to parental cells, but at levels far below those observed in IGF-responsive MCF-7 cells. The transfected cells were also not responsive to IGF-1 in monolayer growth. Thus, IRS-1 expression and activation alone are insufficient to mediate a proliferative response to IGF-1 in breast cancer cells, and it is likely that maximal activation of downstream signaling pathways must also occur. (C) 1999 Harcourt Publishers Ltd.