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HBV integrants of hepatocellular carcinoma cell lines contain an active enhancer.

Abstract：

:Hepatitis B virus (HBV) infection is a major risk factor worldwide for the development of hepatocellular carcinoma (HCC). Integrated HBV DNA fragments, often highly rearranged, are frequently detected in HCC. In woodchuck, the viral enhancer plays a central role in hepatocarcinogenesis, but in humans the mechanism of HBV oncogenesis has not been established. In this study we investigated the status of the viral enhancer in two human HCC cell lines, Hep3B and PLC/PRF/5 each containing one or more integrated HBV DNA fragments. Active enhancer was defined by virtue of its protein occupancy as determined by genomic in vivo DMS footprinting. In PLC/PRF/5 cells, the HBV DNA was integrated in a cellular gene at chromosome 11q13, at a locus reported to be amplified in many tumors. We show here that in both cell lines, the integrated HBV DNA fragments contain an active enhancer-I. In particular, the occupation of the two previously defined basic enhancer elements, E and EP, was prominent. While in both cell lines the same protein binds to the EP elements, the E element, however, is occupied in a cell-line specific manner. In PLC/PRF/5 but not Hep3B, the prominent binding of an undefined protein was detected. Our data suggest that this protein is likely to be the fetoprotein transcription factor (FTF). The finding that enhancer sequences are conserved and functional in different cell lines suggests a selection pressure for their long-term maintenance. We therefore propose that the HBV enhancer-I might play a role in hepatocellular carcinogenesis.

journal_name

Oncogene

journal_title

Oncogene

authors

Shamay M,Agami R,Shaul Y

doi

10.1038/sj.onc.1204879

subject

Has Abstract

pub_date

2001-10-18 00:00:00

pages

6811-9

issue

47

eissn

0950-9232

issn

1476-5594

journal_volume

20

pub_type

杂志文章

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