Transgenic expression of entire hepatitis B virus in mice induces hepatocarcinogenesis independent of chronic liver injury

Bing Na, Zhiming Huang, Qian Wang, Zhongxia Qi, Yongjun Tian, Cheng Chan Lu, Jingwei Yu, Martha A. Hanes, Sanjay Kakar, Eric J. Huang, J. H.James Ou, Limin Liu, T. S.Benedict Yen

研究成果: Article

27 引文 斯高帕斯(Scopus)

摘要

Hepatocellular carcinoma (HCC), the third leading cause of cancer deaths worldwide, is most commonly caused by chronic hepatitis B virus (HBV) infection. However, whether HBV plays any direct role in carcinogenesis, other than indirectly causing chronic liver injury by inciting the host immune response, remains unclear. We have established two independent transgenic mouse lines expressing the complete genome of a mutant HBV ("preS2 mutant") that is found at much higher frequencies in people with HCC than those without. The transgenic mice show evidence of stress in the endoplasmic reticulum (ER) and overexpression of cyclin D1 in hepatocytes. These mice do not show any evidence of chronic liver injury, but by 2 years of age a majority of the male mice develop hepatocellular neoplasms, including HCC. Unexpectedly, we also found a significant increase in hepatocarcinogenesis independent of necroinflammation in a transgenic line expressing the entire wildtype HBV. As in the mutant HBV mice, HCC was found only in aged-2-year-old-mice of the wildtype HBV line. The karyotype in all the three transgenic lines appears normal and none of the integration sites of the HBV transgene in the mice is near an oncogene or tumor suppressor gene. The significant increase of HCC incidence in all the three transgenic lines-expressing either mutant or wildtype HBV-therefore argues strongly that in absence of chronic necroinflammation, HBV can contribute directly to the development of HCC.

原文English
文章編號e26240
期刊PloS one
6
發行號10
DOIs
出版狀態Published - 2011 十月 12

    指紋

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

引用此

Na, B., Huang, Z., Wang, Q., Qi, Z., Tian, Y., Lu, C. C., Yu, J., Hanes, M. A., Kakar, S., Huang, E. J., Ou, J. H. J., Liu, L., & Yen, T. S. B. (2011). Transgenic expression of entire hepatitis B virus in mice induces hepatocarcinogenesis independent of chronic liver injury. PloS one, 6(10), [e26240]. https://doi.org/10.1371/journal.pone.0026240