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Article: Distinct pathways of genomic progression to benign and malignant tumors of the liver

TitleDistinct pathways of genomic progression to benign and malignant tumors of the liver
Authors
Keywordsβ-Catenin
Hepatocellular carcinoma
Hepatocyte nuclear factor 1α
Liver cancer
MET
Mouse
Issue Date2007
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 2007, v. 104 n. 37, p. 14771-14776 How to Cite?
AbstractWe used several of the genetic lesions commonly associated with human liver tumors to reconstruct genetic progression to hepatocellular carcinoma and adenoma in mouse models. We initiated tumorigenesis with a transgene of the protooncogene MET or by hydrodynamic transfection of MET in combination with other genes into the livers of adult animals. Hepatocellular carcinoma in both instances arose from cooperation between MET and constitutively active versions of β-catenin. In contrast, adenomas were produced by cooperation between MET and defective signaling through the transcription factor HNF1α. Prompted by these findings, we uncovered a coincidence between activation of the protein-tyrosine kinase encoded by MET and activating mutations of β-catenin in a subset of human hepatocellular carcinomas. Inactivation of MET transgenes led to regression of hepatocellular carcinomas despite the persistence of activated β-catenin. The tumors eventually recurred in the absence of MET expression, however, presumably after the occurrence of one or more events that cooperated with activated β-catenin in lieu of MET. These results offer insight into hepatic tumorigenesis, provide mouse models that should be useful in the further study of hepatic tumorigenesis and for preclinical testing, and identify a subset of human hepatocellular carcinomas that may be susceptible to combination therapy directed against Met and the Wnt signaling pathway. © 2007 by The National Academy of Sciences of the USA.
Persistent Identifierhttp://hdl.handle.net/10722/84491
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTward, ADen_HK
dc.contributor.authorJones, KDen_HK
dc.contributor.authorYant, Sen_HK
dc.contributor.authorCheung, STen_HK
dc.contributor.authorFan, STen_HK
dc.contributor.authorChen, Xen_HK
dc.contributor.authorKay, MAen_HK
dc.contributor.authorWang, Ren_HK
dc.contributor.authorBishop, MJen_HK
dc.date.accessioned2010-09-06T08:53:35Z-
dc.date.available2010-09-06T08:53:35Z-
dc.date.issued2007en_HK
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 2007, v. 104 n. 37, p. 14771-14776en_HK
dc.identifier.issn0027-8424en_HK
dc.identifier.urihttp://hdl.handle.net/10722/84491-
dc.description.abstractWe used several of the genetic lesions commonly associated with human liver tumors to reconstruct genetic progression to hepatocellular carcinoma and adenoma in mouse models. We initiated tumorigenesis with a transgene of the protooncogene MET or by hydrodynamic transfection of MET in combination with other genes into the livers of adult animals. Hepatocellular carcinoma in both instances arose from cooperation between MET and constitutively active versions of β-catenin. In contrast, adenomas were produced by cooperation between MET and defective signaling through the transcription factor HNF1α. Prompted by these findings, we uncovered a coincidence between activation of the protein-tyrosine kinase encoded by MET and activating mutations of β-catenin in a subset of human hepatocellular carcinomas. Inactivation of MET transgenes led to regression of hepatocellular carcinomas despite the persistence of activated β-catenin. The tumors eventually recurred in the absence of MET expression, however, presumably after the occurrence of one or more events that cooperated with activated β-catenin in lieu of MET. These results offer insight into hepatic tumorigenesis, provide mouse models that should be useful in the further study of hepatic tumorigenesis and for preclinical testing, and identify a subset of human hepatocellular carcinomas that may be susceptible to combination therapy directed against Met and the Wnt signaling pathway. © 2007 by The National Academy of Sciences of the USA.en_HK
dc.languageengen_HK
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_HK
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_HK
dc.subjectβ-Cateninen_HK
dc.subjectHepatocellular carcinomaen_HK
dc.subjectHepatocyte nuclear factor 1αen_HK
dc.subjectLiver canceren_HK
dc.subjectMETen_HK
dc.subjectMouseen_HK
dc.titleDistinct pathways of genomic progression to benign and malignant tumors of the liveren_HK
dc.typeArticleen_HK
dc.identifier.emailSiu, TC: stcheung@hkucc.hku.hken_HK
dc.identifier.authoritySiu, TC=rp00457en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1073/pnas.0706578104en_HK
dc.identifier.pmid17785413en_HK
dc.identifier.scopuseid_2-s2.0-35548966020en_HK
dc.identifier.hkuros140964en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-35548966020&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume104en_HK
dc.identifier.issue37en_HK
dc.identifier.spage14771en_HK
dc.identifier.epage14776en_HK
dc.identifier.isiWOS:000249513000041-
dc.publisher.placeUnited Statesen_HK
dc.identifier.f10001091002-
dc.identifier.scopusauthoridTward, AD=6603125701en_HK
dc.identifier.scopusauthoridJones, KD=7404726684en_HK
dc.identifier.scopusauthoridYant, S=6602719660en_HK
dc.identifier.scopusauthoridSiu, TC=7202473497en_HK
dc.identifier.scopusauthoridSheung, TF=6506234707en_HK
dc.identifier.scopusauthoridChen, X=8978110800en_HK
dc.identifier.scopusauthoridKay, MA=7202188427en_HK
dc.identifier.scopusauthoridWang, R=26025372800en_HK
dc.identifier.scopusauthoridBishop, JM=7402084903en_HK
dc.identifier.citeulike2724085-

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