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FEBS Lett. 2006 Jan 9;580(1):184-90. Epub 2005 Dec 9.

Transformation-associated gene regulation by ATF6alpha during hepatocarcinogenesis.

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Department of Biochemistry II, National Defense Medical College, 3-2 Namiki, Tokorozawa-shi, Saitama 359-8513, Japan.


We have previously reported that the endoplasmic reticulum (ER) stress-regulated transmembrane transcription factor 6 alpha (ATF6alpha) is implicated in the pathogenesis of hepatocellular carcinomas (HCCs). In order to further identify genes that are regulated by ATF6alpha, the global gene expression profiles of the ATF6alpha-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 ATF6alpha, 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.

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