RGD Reference Report - AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. - Rat Genome Database

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AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1.

Authors: Satoh, S  Daigo, Y  Furukawa, Y  Kato, T  Miwa, N  Nishiwaki, T  Kawasoe, T  Ishiguro, H  Fujita, M  Tokino, T  Sasaki, Y  Imaoka, S  Murata, M  Shimano, T  Yamaoka, Y  Nakamura, Y 
Citation: Satoh S, etal., Nat Genet 2000 Mar;24(3):245-50.
RGD ID: 1300371
Pubmed: PMID:10700176   (View Abstract at PubMed)
DOI: DOI:10.1038/73448   (Journal Full-text)

The Wnt signaling pathway is essential for development and organogenesis. Wnt signaling stabilizes beta-catenin, which accumulates in the cytoplasm, binds to 1-cell factor (TCF; also known as lymphocyte enhancer-binding factor, LEF) and then upregulates downstream genes. Mutations in CTNNB1 (encoding beta-catenin) or APC (adenomatous polyposis coli) have been reported in human neoplasms including colon cancers and hepatocellular carcinomas (HCCs). Because HCC5 tend to show accumulation of beta-catenin more often than mutations in CTNNB1, we looked for mutations in AXIN1, encoding a key factor for Wnt signaling, in 6 HCC cell lines and 100 primary HCC5. Among the 4 cell lines and 87 HCC5 in which we did not detect CTNNB1 mutations, we identified AXIN1 mutations in 3 cell lines and 6 mutations in 5 of the primary HCCs. In cell lines containing mutations in either gene, we observed increased DNA binding of TCF associated with beta-catenin in nuclei. Adenovirus mediated gene transfer of wild-type AXINI induced apoptosis in hepatocellular and colorectal cancer cells that had accumulated beta-catenin as a consequence of either APC, CTNNB1 or AXIN1 mutation, suggesting that axin may be an effective therapeutic molecule for suppressing growth of hepatocellular and colorectal cancers.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hepatocellular carcinoma  IAGP 1300371 RGD 
hepatocellular carcinoma  ISOAXIN1 (Homo sapiens)1300371; 1300371 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Axin1  (axin 1)

Genes (Mus musculus)
Axin1  (axin 1)

Genes (Homo sapiens)
AXIN1  (axin 1)


Additional Information