MAPPING OF THE HEPATITIS-B VIRUS GENOME IN HEPATOCELLULAR-CARCINOMA USING PCR AND DEMONSTRATION OF A POTENTIAL TRANSACTIVATOR ENCODED BY THE FREQUENTLY DETECTED FRAGMENT

被引:13
作者
RAMESH, R
PANDA, SK
JAMEEL, S
RAJASAMBANDAM, P
机构
[1] ALL INDIA INST MED SCI,DEPT PATHOL,NEW DELHI 110029,DELHI,INDIA
[2] MADRAS MED COLL & GOVT GEN HOSP,MADRAS,TAMIL NADU,INDIA
[3] ICGEB,NEW DELHI,DELHI,INDIA
关键词
D O I
10.1099/0022-1317-75-2-327
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The association of hepatitis B virus (HBV) infection with hepatocellular carcinoma (HCC) is well established. Insertional mutagenesis, trans-activation by truncated X or preS2/S regions and activation of growth regulatory genes or oncogenes have all been suggested as possible mechanisms for this carcinogenesis. However, no consensus regarding the mechanism or region of the HBV genome involved has been established. Of the 36 HCC tissues analysed for the presence and extent of the HBV genome, using multiple overlapping PCR, 22 (61%) were found to be positive. Twenty of these showed the presence of a fragment (nucleotides 636 to 746) that covered part of the surface antigen gene. The recognized trans-activators, X and preS2/S, were present in only seven (31.8 %) and 12 (54.5 %) cases, respectively. In two cases the entire viral genome was detected. The trans-activation potential of the cloned S fragment(nucleotides 426 to 851) covering the frequently detected fragment (nucleotides 636 to 746) was investigated in cotransfection experiments. This fragment was able to trans-activate the HBV enhancer-X promoter target. To define the specificity of the trans-activation and the sequences involved, frameshift and deletion mutants of this fragment were constructed and analysed. The transactivation activity was lost in the frameshift mutants. The deletion mutants that retained nucleotide sequences 436 to 679 showed trans-activation activity whereas the other ones (nucleotide sequences 436 to 611) did not show any activity. It is suggested that the frequently detected HBV genome fragment belonging to the S gene frame has a trans-activation potential. This may explain the mechanism for pathogenicity of HBV-associated HCC.
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页码:327 / 334
页数:8
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