RRC ID 67185
Author Sasaki M, Ikeda H, Itatsu K, Yamaguchi J, Sawada S, Minato H, Ohta T, Nakanuma Y.
Title The overexpression of polycomb group proteins Bmi1 and EZH2 is associated with the progression and aggressive biological behavior of hepatocellular carcinoma.
Journal Lab Invest
Abstract Polycomb-group proteins Bmi1 and EZH2 are involved in the malignant transformation and biological aggressiveness of several human carcinomas. We herein examined the significance of the Bmi1 and EZH2 expression in hepatocellular carcinoma (HCC) and its preneoplastic lesions, dysplastic nodules. The expression of Bmi1 and EZH2 were examined immunohistochemically in HCC (n=27) and dysplastic nodules (n=14), and combined hepatocellular and cholangiocarcinoma (HC-CC) (n=14). The effect of Bmi1 and EZH2 knockdown was examined in cultured HCC cells (HuH7 and HepG2) using siRNA. It was determined that Bmi1 was constantly expressed in cholangiocytes, but not in hepatocytes, and EZH2 was detected in neither cholangiocytes nor hepatocytes. Bmi1 and EZH2 were overexpressed in HCC and more extensively in HC-CC (P<0.01). Interestingly, Bmi1 and EZH2 were not overexpressed in the dysplastic nodules. The expression of Bmi1 and EZH2 was heterogeneous and associated with vascular infiltration, the histological grades, and the cell proliferation activity in HCC and HC-CC. In cultured carcinoma cells overexpressing Bmi1 and EZH2, knockdown of Bmi1 and EZH2 resulted in decreased cell proliferation activities. Therefore, the overexpression of polycomb-group proteins Bmi1 and EZH2 is associated with the malignant progression of HCC, thereby reflecting the aggressive biological behavior in HCC and HC-CC.
Volume 88(8)
Pages 873-82
Published 2008-8-1
DOI 10.1038/labinvest.2008.52
PII labinvest200852
PMID 18591938
MeSH Aged Aged, 80 and over Bile Duct Neoplasms / metabolism Bile Ducts, Intrahepatic / metabolism Carcinoma, Hepatocellular / metabolism* Carcinoma, Hepatocellular / pathology Cell Line, Tumor Cell Proliferation Cell Transformation, Neoplastic / metabolism* Cholangiocarcinoma / metabolism DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Enhancer of Zeste Homolog 2 Protein Female Humans Immunohistochemistry Liver / metabolism Liver / pathology Liver Neoplasms / metabolism* Liver Neoplasms / pathology Male Middle Aged Neovascularization, Pathologic / metabolism Nuclear Proteins / genetics Nuclear Proteins / metabolism* Polycomb Repressive Complex 1 Polycomb Repressive Complex 2 Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism* RNA, Small Interfering / genetics Repressor Proteins / genetics Repressor Proteins / metabolism* Transcription Factors / genetics Transcription Factors / metabolism*
IF 4.197
Human and Animal Cells Hep G2(RCB1648) HuH-7(RCB1366)