A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä

Pim-1 Kinase Expression Predicts Radiation Response in Squamocellular Carcinoma of Head and Neck and Is under the Control of Epidermal Growth Factor Receptor




TekijätPeltola K, Hollmen M, Maula SM, Rainio E, Ristamaki R, Luukkaa M, Sandholm J, Sundvall M, Elenius K, Koskinen PJ, Grenman R, Jalkanen S

KustantajaNEOPLASIA PRESS

Julkaisuvuosi2009

JournalNeoplasia

Tietokannassa oleva lehden nimiNEOPLASIA

Lehden akronyymiNEOPLASIA

Vuosikerta11

Numero7

Aloitussivu629

Lopetussivu636

Sivujen määrä8

ISSN1522-8002

DOIhttps://doi.org/10.1593/neo.81038

Verkko-osoitehttp://www.ncbi.nlm.nih.gov/pubmed/19568408


Tiivistelmä

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 a. 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.


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