Alteration of the VRK1-p53 autoregulatory loop in human lung carcinomas

Human VRK1 (vaccinia-retated kinase 1) is a novel serine-threonine kinase that VRK1; regulates several transcription factors, including p53, ATF2 and c-Jun; and its toss results in Squamous cell defects of cell proliferation. VRK1 stabilizes p53 and the accumulated p53 downregutates VRK1 carcinoma; forming an autoregulatory loop. Wild-type p53, but not mutant p53, was able to downregutate p53; VRK1 in the A549 Lung carcinoma cell line. VRK1 expression has been studied in human lung p16; carcinomas. VRK1 protein level was significantly higher in squamous cell lung carcinomas than Proliferation 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. (c) 2007 Elsevier Ireland Ltd. All rights reserved.