TY - JOUR
T1 - Deletion of integrated hepatitis B virus genome and cellular flanking sequences in hepatocellular carcinoma cells in BALB/c mice
AU - Chang, Poa Chun
AU - Hu, Cheng Po
AU - Chen, Shu Hsia
AU - Wang-Wuu, Sheng
AU - Chang, Chungming
N1 - Funding Information:
Abbreviations: HBV, hepatitis B virus; HCC, hepatocellular carcinoma; ML, mouse liver; HBsAg, hepatitis B surface antigen; HBc/eAg, hepatitis B c/e antigen. From the 1 Graduate Institute of Microbiology and Immunology, National Yang-Ming University; e Department of Medical Research, Veterans General Hospital, 3 Department of General Studies, National Yang-Ming University, Taipei, Taiwan, Republic of China. Received July 26, 1993; accepted January 20, 1995. This work was supported by grants from the National Sciences Council (NSC81-0419-B075-520, NSC81-0418-B075-04), Republic of China. Address reprint requests to: Chungming Chang, PhD, Graduate Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan, Republic of China. Copyright © 1995 by the American Association for the Study of Liver Diseases. 0270-9139/95/2106-000453.00/0
PY - 1995/6
Y1 - 1995/6
N2 - We have previously reported the establishment of well-differentiated BALB/c mouse liver (ML) cell lines. Transfection of these cell lines with hepatitis B virus (HBV) DNA led to the expression of HBV-specific antigens and integration of HBV sequences in the cellular genome. Two cloned HBV-transfected ML cell lines, ML2(HBV) and ML-3(HBV), expressed viral antigens and were highly tumorigenic in nude mice. However, the tumorigenicity of the two cell lines was significantly reduced in BALB/c mice. Southern blot analyses showed that the integrated HBV sequences were retained in tumors growing in nude mice but deleted in tumors growing in BALB/c mice. Furthermore, the deletion of HBV DNA was accompanied by deletion of chromosomal sequences flanking the HBV integration sites. In ML-2(HBV) cells, a significant reduction in chromosomal number was also observed. These results suggest that the immune response of BALB/c mice selected against hepatocellular carcinoma (HCC) cells expressing viral antigens and led to the proliferation of cells with deleted HBV sequences and concomitant chromosome aberrations. By using this mechanism, HCC cells escape the immune surveillance and gain the advantage of cell growth.
AB - We have previously reported the establishment of well-differentiated BALB/c mouse liver (ML) cell lines. Transfection of these cell lines with hepatitis B virus (HBV) DNA led to the expression of HBV-specific antigens and integration of HBV sequences in the cellular genome. Two cloned HBV-transfected ML cell lines, ML2(HBV) and ML-3(HBV), expressed viral antigens and were highly tumorigenic in nude mice. However, the tumorigenicity of the two cell lines was significantly reduced in BALB/c mice. Southern blot analyses showed that the integrated HBV sequences were retained in tumors growing in nude mice but deleted in tumors growing in BALB/c mice. Furthermore, the deletion of HBV DNA was accompanied by deletion of chromosomal sequences flanking the HBV integration sites. In ML-2(HBV) cells, a significant reduction in chromosomal number was also observed. These results suggest that the immune response of BALB/c mice selected against hepatocellular carcinoma (HCC) cells expressing viral antigens and led to the proliferation of cells with deleted HBV sequences and concomitant chromosome aberrations. By using this mechanism, HCC cells escape the immune surveillance and gain the advantage of cell growth.
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U2 - 10.1016/0270-9139(95)90451-4
DO - 10.1016/0270-9139(95)90451-4
M3 - Article
C2 - 7768493
AN - SCOPUS:0029067531
SN - 0270-9139
VL - 21
SP - 1504
EP - 1509
JO - Hepatology
JF - Hepatology
IS - 6
ER -