Hepatitis C virus core protein stimulates hepatocyte growth: Correlation with upregulation of wnt-1 expression

Takayoshi Fukutomi, Yonghong Zhou, Shigenobu Kawai, Hidetoshi Eguchi, Jack R. Wands, Jisu Li

研究成果: ジャーナルへの寄稿学術誌査読

138 被引用数 (Scopus)

抄録

Hepatitis C virus (HCV) core protein has been implicated in the development of human hepatocellular carcinoma (HCC). Here we report that expression of HCV core protein by transient transfection increased cell proliferation, DNA synthesis, and cell cycle progression in Huh-7 cells, a human HCC-derived cell line. Culture supernatant from transfected cells also harbored a growth-promoting effect. Moreover, a full-length HCV replicon, but not a subgenomic replicon devoid of the core gene, significantly stimulated growth of transiently transfected Huh-7.5 cells. However, growth of the subgenomic replicon-containing Huh-7.5 cells could be stimulated by secondary transfection with core gene but not other structural genes present in the full-length replicon. Microarray analysis revealed threefold or more transcriptional changes in 372 of 12,500 known human genes in core protein expressing Huh-7 cells, with most genes involved in cell growth or oncogenic signaling, being upregulated rather than downregulated. Of particular interest is the marked upregulation of both wnt-1 and its downstream target gene WISP-2. Indeed, small interfering RNA against wnt-1 blunted growth stimulation by core gene, whereas transfection of Huh-7 cells with the wnt-1 gene sufficed to promote cell proliferation. Consistent with secretion of the wnt-1 protein, conditioned medium from wnt-1 transfected cells accelerated cell growth. In conclusion, HCV core protein induces Huh-7 cell proliferation whether alone or in the context of HCV replication, which is at least partly mediated by transcriptional upregulation of growth-related genes, in particular wnt-1.

本文言語英語
ページ(範囲)1096-1105
ページ数10
ジャーナルHepatology
41
5
DOI
出版ステータス出版済み - 5月 2005
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 肝臓学

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