Expression of transforming growth factor alpha in human hepatocellular carcinoma.
Transforming growth factor alpha (TGF-alpha) is a mitogenic polypeptide which acts on the epidermal growth factor receptor (EGFR). The aim of this study was to examine the expression of TGF-alpha in human hepatocellular carcinoma (HCC) and surrounding cirrhotic tissue, and to compare it with normal liver. Immunoreactive TGF-alpha was detected using two antibodies raised against its C terminus, a polyclonal antibody 26T and a monoclonal antibody Ab-2. In normal liver immunoreactive TGF-alpha was localised strongly to bile duct epithelium and weakly in occasional parenchymal cells but was notably absent from perisinusoidal and Kupffer cells. Eight out of twenty-eight (28%) cases of HCC expressed TGF-alpha as demonstrated by cytoplasmic staining with both antibodies and in four cases additional membrane immunoreactivity was demonstrated using 26T. However, where cirrhotic tissue surrounding TGF-alpha positive tumours was available for analysis immunoreactive TGF-alpha was detected in only 1/7 cases. TGF-alpha synthesis by malignant hepatocytes was supported by the detection of specific RNA by Northern blotting from two cases with TGF-alpha immunoreactivity. These results implicate bile duct epithelium as an important source of TGF-alpha in human liver. Furthermore, in HCC the expression of TGF-alpha in some cases, together with paucity of TGF-alpha immunoreactivity in surrounding cirrhotic tissue, suggests that TGF-alpha may play a role in continued cell proliferation in human hepatocarcinogenesis.
Department of Medicine, University of Newcastle upon Tyne, UK.
J D
JD
Collier
K
K
Guo
W J
WJ
Gullick
M F
MF
Bassendine
A D
AD
Burt
D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics*; D016211:Transforming Growth Factor alpha / Q000235:genetics*
D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha