Pim-1 Kinase Expression Predicts Radiation Response in Squamocellular Carcinoma of Head and Neck and Is under the Control of Epidermal Growth Factor Receptor. Neoplasia (New York, N.Y.) [Neoplasia] Journal article | | Title | Pim-1 Kinase Expression Predicts Radiation Response in Squamocellular Carcinoma of Head and Neck and Is under the Control of Epidermal Growth Factor Receptor. | | Author(s) | Peltola K, Hollmen M, Maula SM, Rainio E, Ristamäki R, Luukkaa M, Sandholm J, Sundvall M, Elenius K, Koskinen PJ, Grenman R, Jalkanen S | | Institution | Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland. | | Source | Neoplasia 2009 Jul; 11(7):629-36. | | Abstract | Pim-1 is an oncogenic serine/threonine kinase with poorly defined function in epithelial cancers. In this study, we determined 1) associations of Pim-1 expression with clinicopathological parameters including responsiveness to irradiation in squamocellular cancers of head and neck and 2) how Pim-1 expression is controlled subsequent to irradiation. Moderate to high expression of Pim-1 correlated to poor response to radiation therapy (P = .003). It is also associated to the expression of epidermal growth factor receptor (EGFR, P < .0001), which has been shown to be activated by irradiation. In radioresistant tumors, irradiation promoted nuclear translocation of Pim-1 (P < .005). When directly testing EGFR dependence of Pim-1 expression, up-regulation and nuclear translocation of Pim-1 could be induced through stimulation of EGFR with its ligands EGF or transforming growth factor alpha. Both ligand- and irradiation-induced changes in Pim-1 expression and localization could be inhibited by the monoclonal anti-EGFR antibody cetuximab and by the tyrosine kinase inhibitor gefitinib also targeting EGFR. These results suggest that irradiation-induced activation of EGFR upregulates Pim-1, and Pim-1 may be used as a novel predictive marker of radiation response in patients with squamocellular cancers of head and neck. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 19568408 |
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