Transformation-associated gene regulation by ATF6α during hepatocarcinogenesis

We have previously reported that the endoplasmic reticulum (ER) stress-regulated transmembrane transcription factor 6 α (ATF6α) is implicated in the pathogenesis of hepatocellular carcinomas (HCCs). In order to further identify genes that are regulated by ATF6α, the global gene expression profiles of the ATF6α-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 ATF6α, 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.