Transformation-associated gene regulation by ATF6alpha during hepatocarcinogenesis.
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.
Arai
Masaaki
M
Department of Biochemistry II, National Defense Medical College, 3-2 Namiki, Tokorozawa-shi, Saitama 359-8513, Japan.
Kondoh
Nobuo
N
Imazeki
Nobuo
N
Hada
Akiyuki
A
Hatsuse
Kazuo
K
Kimura
Fumihiro
F
Matsubara
Osamu
O
Mori
Kazutoshi
K
Wakatsuki
Toru
T
Yamamoto
Mikio
M
D051702:Activating Transcription Factor 6 / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D050436:Regulatory Elements, Transcriptional / Q000235:genetics
C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; D009363:Neoplasm Proteins