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Growth Factors. 2011 Dec;29(6):278-89. doi: 10.3109/08977194.2011.616200. Epub 2011 Sep 13.

Differential expression and signaling activation of insulin receptor isoforms A and B: A link between breast cancer and diabetes.

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Breast Cancer Laboratory, Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, CA 92350, USA.


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.

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