Transformation-associated gene regulation by ATF6α during hepatocarcinogenesis

We have previously reported that the endoplasmic reticulum (ER) stress-regulated transmembrane transcription factor 6 alpha (ATF6 alpha) is implicated in the pathogenesis of hepatocellular carcinomas (HCCs). In order to further identify genes that are regulated by ATF6 alpha, the global gene expression profiles of the ATF6 alpha-transfected and untransfected HCC cell line, HLF, were analyzed. These results were then compared with the differential gene expression patterns of poorly differentiated HCC and control non-tumorous liver tissue. Our findings demonstrate that at least 18 genes are specifically upregulated by ATF6 alpha, while another UPR mediator, XBP1 or ER-stress inducer, thapsigargin could partially stimulate or even repress some of them in HCC cells. Moreover, six of these identified genes contain potential ER stress-responsive elements and/or unfolded protein response elements in their 5' regulatory regions. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.