Kalla Singh S, Brito C, Tan Q W, De León M, De León D
Breast Cancer Laboratory, Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, CA 92350, USA.
Growth Factors. 2011 Dec;29(6):278-89. doi: 10.3109/08977194.2011.616200. Epub 2011 Sep 13.
We showed that when insulin-like growth factor II (IGF-II) is highly expressed in breast tissues and cell lines, the IGF-I receptor signaling pathway is highly activated. Since IGF-II activates the insulin receptor (INSR), we propose that the INSR signaling is also activated in this system. We examined the expression of both INSR isoforms, insulin receptor A (INSR-A) and insulin receptor B (INSR-B), and the downstream signaling pathways in breast cancer (BC) cells and in paired (normal/tumor) breast tissues from 100 patients. Analysis was performed by real-time PCR, Western blot, immunohistochemistry, and phospho-ELISA techniques. Tumor tissues and cell lines from African-American patients expressed higher levels of INSR-A, but lower levels of INSR-B. Accordingly, insulin receptor substrate 1 and focal adhesion kinase activation were significantly increased in these women. We conclude that higher INSR-A and lower INSR-B contribute to higher proliferation and lower metabolic response. Thus, differential expression of INSR isoforms represents a potential biological link between BC and diabetes.
我们发现，当胰岛素样生长因子II（IGF-II）在乳腺组织和细胞系中高表达时，IGF-I受体信号通路会被高度激活。由于IGF-II能激活胰岛素受体（INSR），我们推测INSR信号在该系统中也被激活。我们检测了100例患者乳腺癌（BC）细胞及配对的（正常/肿瘤）乳腺组织中两种INSR亚型，即胰岛素受体A（INSR-A）和胰岛素受体B（INSR-B）的表达情况以及下游信号通路。采用实时PCR、蛋白质免疫印迹、免疫组织化学和磷酸化酶联免疫吸附测定技术进行分析。非裔美国患者的肿瘤组织和细胞系中INSR-A表达水平较高，但INSR-B表达水平较低。相应地，这些女性体内的胰岛素受体底物1和粘着斑激酶激活水平显著升高。我们得出结论，较高的INSR-A和较低的INSR-B导致了更高的增殖率和更低的代谢反应。因此，INSR亚型的差异表达代表了BC与糖尿病之间潜在的生物学联系。
