Expression of heparin-binding epidermal growth factor in human hepatocellular carcinoma.
OBJECTIVE
Growth factors are involved in the development and progression of cancer. The purpose of this study was to evaluate the possible role of heparin-binding epidermal growth factor-like growth factor (HB-EGF), which is a member of the EGF family, in the neoplastic transformation of hepatocytes.


METHODS
Gene expression and protein production of HB-EGF were investigated in samples of human hepatocellular carcinoma (HCC) from 17 patients using Northern hybridization and immunohistochemical methods.


RESULTS
The amount of HB-EGF messenger RNA was increased in the patients' HCC specimens compared with the surrounding liver tissues. In noncancerous hepatic tissues, HB-EGF was faintly positive in hepatocytes. Immunoreactive HB-EGF-producing cells were identified in HCC cells of all 17 patients with HCC, indicating that HB-EGF was produced in HCC cells themselves. However, none of the specimens from 10 patients with metastatic adenocarcinoma in the liver was positive for HB-EGF. The EGF receptor, which binds to HB-EGF, was also expressed on HCC cells.


CONCLUSIONS
It is hypothesized that the enhanced expression of immunoreactive HB-EGF on the cell suggests a possible role of HB-EGF in the development or progression of human HCC in an autocrine and/or a juxtacrine manners.
Second Department of Internal Medicine, Osaka University Medical School, Japan.
Y
Y
Inui
S
S
Higashiyama
S
S
Kawata
S
S
Tamura
J
J
Miyagawa
N
N
Taniguchi
Y
Y
Matsuzawa
D000328:Adult; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006493:Heparin / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism
C587883:HBEGF protein, human; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D006493:Heparin; D066246:ErbB Receptors