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.
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.
authors: Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland.
authors: Katriina
authors: K
authors: Peltola
authors: Maija
authors: M
authors: Hollmen
authors: Sanna-Mari
authors: SM
authors: Maula
authors: Eeva
authors: E
authors: Rainio
authors: Raija
authors: R
authors: Ristamäki
authors: Marjaana
authors: M
authors: Luukkaa
authors: Jouko
authors: J
authors: Sandholm
authors: Maria
authors: M
authors: Sundvall
authors: Klaus
authors: K
authors: Elenius
authors: Päivi J
authors: PJ
authors: Koskinen
authors: Reidar
authors: R
authors: Grenman
authors: Sirpa
authors: S
authors: Jalkanen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D066246:ErbB Receptors / Q000378:metabolism* / Q000528:radiation effects; D005455:Fluorescent Antibody Technique; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D051573:Proto-Oncogene Proteins c-pim-1 / Q000096:biosynthesis*; D011836:Radiation Tolerance / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D051573:Proto-Oncogene Proteins c-pim-1