Pim-1 kinase expression predicts radiation response in squamocellular carcinoma of head and neck and is under the control of epidermal growth factor receptor.
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.
Peltola
Katriina
K
Turku Centre for Biotechnology, University of Turku and Abo Akademi University, Turku, Finland.
Hollmen
Maija
M
Maula
Sanna-Mari
SM
Rainio
Eeva
E
Ristamäki
Raija
R
Luukkaa
Marjaana
M
Sandholm
Jouko
J
Sundvall
Maria
M
Elenius
Klaus
K
Koskinen
Päivi J
PJ
Grenman
Reidar
R
Jalkanen
Sirpa
S
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*
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D051573:Proto-Oncogene Proteins c-pim-1