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Integration of the hepatitis B virus X fragment in hepatocellular carcinoma and its effects on the expression of multiple molecules: a key to the cell cycle and apoptosis.
Int J Oncol 2005; 26(2):467-73IJ

Abstract

We investigated hepatitis B virus (HBV) DNA integration and expression of several proteins involved in the cell cycle and apoptosis, including cyclin A, retinoblastoma protein (pRB), Fas-associated death domain protein (FADD), tumor necrosis factor receptor-associated death domain protein (TRADD), and nuclear factor kappaB (NF-kappaB) in HBV-associated hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Archival HCC and LC specimens were obtained from 35 patients each with HBV infection; 5 normal liver specimens used as controls were also obtained. Polymerase chain reaction and Southern blot hybridization were used to detect the integration of HBV DNA in the HCC and LC specimens. The protein levels were determined by Western blot assay. The difference in HBV DNA integration between HCC and LC and correlation between HBV-encoded X protein (Hbx) integration and protein expression were analyzed statistically. HBV DNA was detected in 33 (94%) of the HCC and LC specimens. HBx integration differed in the HCC [24 (69%)] and LC [14 (40%)] specimens (p=0.015). Sixty percent of the HCC specimens and 6% of the LC specimens had increased cyclin A expression. Also, 34, 37, 69, and 77% of the HCC specimens were positive for pRB, FADD, TRADD, and NF-kappaB expression, whereas 80, 60, 100, and 100% of the LC specimens were positive for pRB, FADD, TRADD, and NF-kappaB expression. Significant correlations between HBx integration and the level of expression of cyclin A (r=0.452; p=0.006), pRB (r=-0.419; p=0.012), and TRADD (r=0.470; p=0.004) were discovered. Therefore, integration of HBV DNA occurred frequently in HCC and LC cases with chronic HBV infection, whereas HBx integration occurred more often in HCC than in LC cases (p=0.015). HBx integration and altered expression of genes is a key to apoptosis and may play important roles in HBV-induced hepatocarcinogenesis.

Authors+Show Affiliations

Department of General Surgery, Shanghai Jiaotong University Affiliated Shanghai First People's Hospital, Shanghai 200080, P.R. China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15645132

Citation

Peng, Zhihai, et al. "Integration of the Hepatitis B Virus X Fragment in Hepatocellular Carcinoma and Its Effects On the Expression of Multiple Molecules: a Key to the Cell Cycle and Apoptosis." International Journal of Oncology, vol. 26, no. 2, 2005, pp. 467-73.
Peng Z, Zhang Y, Gu W, et al. Integration of the hepatitis B virus X fragment in hepatocellular carcinoma and its effects on the expression of multiple molecules: a key to the cell cycle and apoptosis. Int J Oncol. 2005;26(2):467-73.
Peng, Z., Zhang, Y., Gu, W., Wang, Z., Li, D., Zhang, F., ... Xie, K. (2005). Integration of the hepatitis B virus X fragment in hepatocellular carcinoma and its effects on the expression of multiple molecules: a key to the cell cycle and apoptosis. International Journal of Oncology, 26(2), pp. 467-73.
Peng Z, et al. Integration of the Hepatitis B Virus X Fragment in Hepatocellular Carcinoma and Its Effects On the Expression of Multiple Molecules: a Key to the Cell Cycle and Apoptosis. Int J Oncol. 2005;26(2):467-73. PubMed PMID: 15645132.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Integration of the hepatitis B virus X fragment in hepatocellular carcinoma and its effects on the expression of multiple molecules: a key to the cell cycle and apoptosis. AU - Peng,Zhihai, AU - Zhang,Yi, AU - Gu,Wei, AU - Wang,Zhaowen, AU - Li,Dapeng, AU - Zhang,Fang, AU - Qiu,Guoqiang, AU - Xie,Keping, PY - 2005/1/13/pubmed PY - 2005/7/27/medline PY - 2005/1/13/entrez SP - 467 EP - 73 JF - International journal of oncology JO - Int. J. Oncol. VL - 26 IS - 2 N2 - We investigated hepatitis B virus (HBV) DNA integration and expression of several proteins involved in the cell cycle and apoptosis, including cyclin A, retinoblastoma protein (pRB), Fas-associated death domain protein (FADD), tumor necrosis factor receptor-associated death domain protein (TRADD), and nuclear factor kappaB (NF-kappaB) in HBV-associated hepatocellular carcinoma (HCC) and liver cirrhosis (LC). Archival HCC and LC specimens were obtained from 35 patients each with HBV infection; 5 normal liver specimens used as controls were also obtained. Polymerase chain reaction and Southern blot hybridization were used to detect the integration of HBV DNA in the HCC and LC specimens. The protein levels were determined by Western blot assay. The difference in HBV DNA integration between HCC and LC and correlation between HBV-encoded X protein (Hbx) integration and protein expression were analyzed statistically. HBV DNA was detected in 33 (94%) of the HCC and LC specimens. HBx integration differed in the HCC [24 (69%)] and LC [14 (40%)] specimens (p=0.015). Sixty percent of the HCC specimens and 6% of the LC specimens had increased cyclin A expression. Also, 34, 37, 69, and 77% of the HCC specimens were positive for pRB, FADD, TRADD, and NF-kappaB expression, whereas 80, 60, 100, and 100% of the LC specimens were positive for pRB, FADD, TRADD, and NF-kappaB expression. Significant correlations between HBx integration and the level of expression of cyclin A (r=0.452; p=0.006), pRB (r=-0.419; p=0.012), and TRADD (r=0.470; p=0.004) were discovered. Therefore, integration of HBV DNA occurred frequently in HCC and LC cases with chronic HBV infection, whereas HBx integration occurred more often in HCC than in LC cases (p=0.015). HBx integration and altered expression of genes is a key to apoptosis and may play important roles in HBV-induced hepatocarcinogenesis. SN - 1019-6439 UR - https://www.unboundmedicine.com/medline/citation/15645132/Integration_of_the_hepatitis_B_virus_X_fragment_in_hepatocellular_carcinoma_and_its_effects_on_the_expression_of_multiple_molecules:_a_key_to_the_cell_cycle_and_apoptosis_ L2 - http://www.spandidos-publications.com/ijo/26/2/467 DB - PRIME DP - Unbound Medicine ER -