Inflammation and IGF-I activate the Akt pathway in breast cancer
| Autor: | Lei Ying, Stefan Ambs, Brenda J. Boersma, Dong H. Lee, David A. Wink, John R. Cottrell, Douglas D. Thomas, Robyn L. Prueitt, Julie E. Goodman, Lorne J. Hofseth, Harris G. Yfantis, Candice M. Pfiester, Tiffany M. Howe, Alan T. Remaley |
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| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
medicine.medical_specialty business.industry medicine.medical_treatment IGFBP3 macromolecular substances medicine.disease Proinflammatory cytokine Insulin-like growth factor Breast cancer Endocrinology Oncology Internal medicine Cancer cell medicine Cancer research Phosphorylation business Protein kinase B PI3K/AKT/mTOR pathway |
| Zdroj: | International Journal of Cancer. 120:796-805 |
| ISSN: | 0020-7136 |
| DOI: | 10.1002/ijc.22336 |
| Popis: | Akt signaling may promote breast cancer progression and poor disease outcome. We hypothesized that serum insulin-like growth factor I (IGF-I) and a proinflammatory tumor environment induce phosphorylation of Akt and downstream targets of Akt in breast cancer. We studied the relationship between Akt pathway activation, IGF-I and markers of inflammation, e.g., nitric oxide synthase-2 (NOS2), cyclooxygenase-2 (COX2) and tumor phagocyte density, in 248 breast tumors. We also examined the association of Akt phosphorylation with breast cancer survival. We observed that phosphorylation of Akt, BAD and caspase-9 correlated strongly with the expression of the 2 proinflammatory enzymes, NOS2 and COX2, in breast tumors (p < 0.001; Spearman rank correlation). Both NOS2 and COX2 expression were independently associated with Akt phosphorylation in the multivariate analysis. Serum IGF-I concentrations and the IGF-I/IGFBP3 ratio correlated with Akt phosphorylation at Thr308 and Ser473 in breast tumors (p |
| Databáze: | OpenAIRE |
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