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The hepatitis B virus X protein promotes tumor cell invasion by inducing membrane-type matrix metalloproteinase-1 and cyclooxygenase-2 expression

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dc.creator Lara-Pezzi, Enrique
dc.creator Gómez Gaviro, María Victoria
dc.creator Gálvez, Beatriz G.
dc.creator Mira, Emilia
dc.creator Iñiguez, Miguel Ángel
dc.creator Fresno, Manuel
dc.creator Martínez-Alonso, Carlos
dc.creator Arroyo, Alicia G.
dc.creator López Cabrera, Manuel
dc.date 2008-04-15T12:16:42Z
dc.date 2008-04-15T12:16:42Z
dc.date 2002-12
dc.date.accessioned 2017-01-31T01:02:20Z
dc.date.available 2017-01-31T01:02:20Z
dc.identifier The Journal of Clinical Investigation, 110,pp.1831–1838, (2002)
dc.identifier 0021-9738
dc.identifier http://hdl.handle.net/10261/3592
dc.identifier 10.1172/JCI200215887.
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3592
dc.description Hepatocellular carcinoma is strongly associated with chronic infection by the hepatitis B virus (HBV) and has poor prognosis due to intrahepatic metastasis. HBx is often the only HBV protein detected in hepatic tumor cells; however, its contribution to tumor invasion and metastasis has not been established so far. In this work, we show that HBx enhances tumor cell invasion, both in vivo and in vitro. The increased invasive capacity induced by HBx is mediated by an upregulation of membrane-type 1 matrix metalloproteinase (MT1-MMP) expression, which in turn activates matrix metalloproteinase-2. Induction of both MT1-MMP expression and cell invasion by HBx is dependent on cyclooxygenase-2 (COX-2) activity. In addition, HBx upregulates the expression of COX-2, which is mediated by the transcriptional activation of the COX-2 gene promoter in a nuclear factor of activated T cell–dependent (NF-AT–dependent) manner. These results demonstrate the ability of HBx to promote tumor cell invasion by a mechanism involving the upregulation of MT1-MMP and COX-2 and provide new insights into the mechanism of action of this viral protein and its involvement in tumor metastasis and recurrence of hepatocellular carcinoma.
dc.description Peer reviewed
dc.format 1417165 bytes
dc.format application/pdf
dc.language eng
dc.publisher American Society for Clinical Investigation
dc.rights openAccess
dc.title The hepatitis B virus X protein promotes tumor cell invasion by inducing membrane-type matrix metalloproteinase-1 and cyclooxygenase-2 expression
dc.type Artículo


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