title: Differential expression and signaling activation of insulin receptor isoforms A and B: A link between breast cancer and diabetes.
abstract: 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.
authors.affiliation: Breast Cancer Laboratory, Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, CA 92350, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kalla Singh
authors.forename: C
authors.initials: C
authors.lastname: Brito
authors.forename: Q W
authors.initials: QW
authors.lastname: Tan
authors.forename: M
authors.initials: M
authors.lastname: De León
authors.forename: D
authors.initials: D
authors.lastname: De León
mesh_terms: D001741:Black or African American; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism*; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D011972:Receptor, Insulin / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D044465:White People
chemical_list: D015703:Antigens, CD; D020033:Protein Isoforms; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; C435941:INSR protein, human; D011972:Receptor, Insulin; D051416:Focal Adhesion Protein-Tyrosine Kinases