IRS1 is highly expressed in localized breast tumors and regulates the sensitivity of breast cancer cells to chemotherapy, while IRS2 is highly expressed in invasive breast tumors.
IRS1 is highly expressed in localized breast tumors and regulates the sensitivity of breast cancer cells to chemotherapy, while IRS2 is highly expressed in invasive breast tumors.
复制标题
DOI：
10.1016/j.canlet.2013.03.030
复制
发表时间：
2013-09-28
期刊：
影响因子：
9.7
通讯作者：
Keegan, Achsah D.
中科院分区：
文献类型：
--
作者：
Porter, Holly A.;Perry, Anthony;Kingsley, Chris;Tran, Nhan L.;Keegan, Achsah D.
胰岛素受体底物（IRS）蛋白已被证明在乳腺癌中发挥重要作用，差异调节癌细胞的生存，增殖和运动。此外，IL-4诱导的转录因子STAT 6的酪氨酸磷酸化显示出保护乳腺癌细胞免于凋亡。在这里，我们分析了人乳腺癌组织的IRS 1，IRS 2，STAT 6和酪氨酸磷酸化STAT 6（pSTAT 6）的表达。我们发现IRS 1和pSTAT 6在导管原位癌（DCIS）中均呈高表达。另一方面，IRS 2在DCIS中表达较低，但与肿瘤侵袭性相关显著增加。我们利用具有不同IRS 1表达的细胞系，MDA-MB-231，MCF 7和MCF 7细胞，由于shRNA慢病毒感染而使IRS 1耗尽，以检查IRS 1和IRS 2在乳腺癌细胞对化疗的反应性中的作用。我们报告说，高IRS 1敏感MCF 7细胞特异性化疗药物。这些结果表明，高IRS 1与低IRS 2表达可能预测乳腺癌中特定类型化疗的有效性。
Insulin receptor substrate (IRS) proteins have been shown to play an important role in breast cancer by differentially regulating cancer cell survival, proliferation, and motility. Furthermore, the IL-4-induced tyrosine phosphorylation of the transcription factor STAT6 was shown to protect breast cancer cells from apoptosis. Here, we analyzed human breast cancer tissues for the expression of IRS1, IRS2, STAT6, and tyrosine phosphorylated STAT6 (pSTAT6). We found that IRS1 and pSTAT6 were both highly expressed in ductal carcinoma in situ (DCIS). On the other hand, IRS2 expression was low in DCIS, but increased significantly in relation to tumor invasiveness. We utilized cell lines with disparate IRS1 expression, MDA-MB-231, MCF7, and MCF7 cells with depleted IRS1 due to shRNA lentiviral infection, to examine the role of IRS1 and IRS2 in the responsiveness of breast cancer cells to chemotherapy. We report that high IRS1 sensitized MCF7 cells to specific chemotherapeutic agents. These results suggest that high IRS1 with low IRS2 expression may predict the effectiveness of specific types of chemotherapy in breast cancer.
登录
查看更多内容
影响因子：
8
作者：
Jackson, JG;Zhang, XH;Yee, D
通讯作者：
Yee, D
影响因子：
4.8
作者：
Molloy, CA;May, FEB;Westley, BR
通讯作者：
Westley, BR
DOI：
10.1186/1478-811x-7-14
发表时间：
2009-06-17
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Mardilovich K;Pankratz SL;Shaw LM
通讯作者：
Shaw LM
影响因子：
4.8
作者：
Jackson, JG;White, MF;Yee, D
通讯作者：
Yee, D
影响因子：
8.8
作者：
Byron, S. A.;Horwitz, K. B.;Richer, J. K.;Lange, C. A.;Zhang, X.;Yee, D.
通讯作者：
Yee, D.