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Expression of HNF‐1α and HNF‐1β in various histological differentiations of hepatocellular carcinoma
Author(s) -
Wang Weiping,
Hayashi Yoshitake,
Ninomiya Toshiaki,
Ohta Kyosuke,
Nakabayashi Hidekazu,
Tamaoki Taiki,
Itoh Hiroshi
Publication year - 1998
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199803)184:3<272::aid-path4>3.0.co;2-k
Subject(s) - hccs , hepatocellular carcinoma , immunohistochemistry , hepatocyte nuclear factors , hepatocyte nuclear factor 4 , transcription factor , biology , pathology , cellular differentiation , cancer research , gene , medicine , genetics , nuclear receptor
Hepatic nuclear factor 1 (HNF‐1) regulates genes in a hepatocyte‐specific manner. It has been previously reported that the ratio of HNF‐1α and HNF‐1β mRNA is related to histological differentiation hepatocellular carcinoma (HCC). In this study, the expression levels of the HNF‐1α and HNF‐1β proteins were analysed relatively and quantitatively in various histologically differentiated HCC and surrounding non‐cancerous tissues, and HNF‐1α binding activity for the AT element of the B domain of the human α‐fetoprotein enhancer was examined. Western blot analysis demonstrated that HNF‐1α protein was expressed at a higher level in well‐differentiated HCC tissues than in the surrounding non‐HCC tissues; on the other hand, the HNF‐1α protein was expressed at lower levels in moderately and poorly differentiated HCCs than in the surrounding non‐HCC tissues. The levels of HNF‐1β expression in well‐differentiated and poorly differentiated HCCs were similar to and higher than those found in the respective surrounding non‐cancerous portions. In binding assays, HNF‐1 binding activity was high in well‐differentiated HCC and lower in moderately and poorly differentiated HCCs. Most well‐differentiated HCC cases showed immunohistochemical expression of HNF‐1α. These findings show that poor histological differentiation of HCC correlates with decreases in the level and activity of HNF‐1α proteins. © 1998 John Wiley & Sons, Ltd.