Lung Cancer (2007) 58, 303—309 available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/lungcan Alteration of the VRK1-p53 autoregulatory loop in human lung carcinomas Alberto Valbuena a,1 , Ana Su´ arez-Gauthier b,1 , Fernando L´ opez-Rios c , Angel L´ opez-Encuentra d , Sandra Blanco a , Pedro L. Fern´ andez e , Montserrat S´ anchez-C´ espedes b , Pedro A. Lazo a,* a Programa de Oncolog´ ıa Translacional, Instituto de Biolog´ ıa Molecular y Celular del C´ ancer, CSIC, Universidad de Salamanca, Spain b Programa de Patolog´ ıa Molecular, Centro Nacional de Investigaciones Oncol´ ogicas (CNIO), Madrid, Spain c Departamento de Anatom´ ıa Patol´ ogica, Hospital Universitario 12 de Octubre, Madrid, Spain d Servicio de Neumolog´ ıa, Hospital Universitario 12 de Octubre, Madrid, Spain e Institut d’Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Departamento de Anatom´ ıa Patol´ ogica, Hospital Clinic, Barcelona, Spain Received 22 March 2007; received in revised form 21 June 2007; accepted 25 June 2007 KEYWORDS VRK1; Squamous cell carcinoma; p53; p16; Proliferation Summary Human VRK1 (vaccinia-related kinase 1) is a novel serine—threonine kinase that regulates several transcription factors, including p53, ATF2 and c-Jun; and its loss results in defects of cell proliferation. VRK1 stabilizes p53 and the accumulated p53 downregulates VRK1 forming an autoregulatory loop. Wild-type p53, but not mutant p53, was able to downregulate VRK1 in the A549 lung carcinoma cell line. VRK1 expression has been studied in human lung carcinomas. VRK1 protein level was significantly higher in squamous cell lung carcinomas than in adenocarcinomas, and inversely correlated with p16. Tumours with p53 mutations have a positive trend with those having very high levels of VRK1 protein, particularly in squamous cell lung carcinomas. These data indicate that the VRK1-p53 autoregulatory loop was not functional in a group of lung carcinomas. The accumulation of VRK1 in tumours with mutant p53 could result in stimulation of other signalling pathways that can contribute to tumour growth and progression in addition to those resulting from loss of p53 function. © 2007 Elsevier Ireland Ltd. All rights reserved. Abbreviations: SCC, squamous cell carcinoma; ADC, adenocarcinoma ∗ Corresponding author at: Centro de Investigaci´ on del C´ ancer, CSIC, Universidad de Salamanca, Campus Miguel de Unamuno, E-37007 Salamanca, Spain. Tel.: +34 923 294 804; fax: +34 923 294 795. E-mail address: plazozbi@usal.es (P.A. Lazo). 1 These authors contributed equally to this work. 0169-5002/$ — see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.lungcan.2007.06.023