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
Tekijät: Peltola K, Hollmen M, Maula SM, Rainio E, Ristamaki R, Luukkaa M, Sandholm J, Sundvall M, Elenius K, Koskinen PJ, Grenman R, Jalkanen S
Kustantaja: NEOPLASIA PRESS
Julkaisuvuosi: 2009
Journal: Neoplasia
Tietokannassa oleva lehden nimi: NEOPLASIA
Lehden akronyymi: NEOPLASIA
Vuosikerta: 11
Numero: 7
Aloitussivu: 629
Lopetussivu: 636
Sivujen määrä: 8
ISSN: 1522-8002
DOI: https://doi.org/10.1593/neo.81038
Verkko-osoite: http://www.ncbi.nlm.nih.gov/pubmed/19568408
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.
Ladattava julkaisu This is an electronic reprint of the original article. |