We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

We 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 beta-catenin. In contrast, adenomas were produced by cooperation between MET and defective signaling through the transcription factor HNF1alpha. Prompted by these findings, we uncovered a coincidence between activation of the protein-tyrosine kinase encoded by MET and activating mutations of beta-catenin in a subset of human hepatocellular carcinomas. Inactivation of MET transgenes led to regression of hepatocellular carcinomas despite the persistence of activated beta-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 beta-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.

Pubmed ID: 17785413 RIS Download

Mesh terms: Adenoma, Liver Cell | Animals | Carcinoma, Hepatocellular | Disease Models, Animal | Gene Expression Regulation, Neoplastic | Hepatocyte Nuclear Factor 1-alpha | Humans | Liver Neoplasms, Experimental | Mice | Mice, Transgenic | Mutation | Precipitin Tests | Proto-Oncogene Proteins c-met | Sequence Analysis, DNA | Transfection | Transgenes | beta Catenin

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

Associated grants

  • Agency: NIDDK NIH HHS, Id: DK49022
  • Agency: NIGMS NIH HHS, Id: T32 GM007618
  • Agency: PHS HHS, Id: 5T32GMO7618
  • Agency: NCI NIH HHS, Id: T32 CA009043
  • Agency: NIDDK NIH HHS, Id: R01 DK049022
  • Agency: PHS HHS, Id: K01 096774
  • Agency: NCI NIH HHS, Id: CA009043

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.