Systematic name M1281
Brief description Cluster PAM5: genes changed exclusively in hepatocellular carcinoma (HCC) samples from 27 month old mice deficient for TXNIP [GeneID=10628].
Full description or abstract The molecular pathogenesis and the genetic aberrations that lead to the progression of hepatocellular carcinoma (HCC) are largely unknown. Here, we demonstrate that the thioredoxin interacting protein (Txnip) gene is a candidate tumor suppressor gene in vivo. We previously showed that the recombinant inbred congenic strain HcB-19 has a spontaneous mutation of the Txnip gene, and we now show that the strain has dramatically increased incidence of HCC, and that the HCC cosegregates with the Txnip mutation. Approximately 40% of the Txnip-deficient mice developed hepatic tumors with an increased prevalence in male mice. Visible tumors develop as early as 8 months of age. Histological analysis confirmed the morphology of HCC in the Txnip-deficient mice. Molecular markers of HCC, alpha-fetoprotein and p53, were increased in tumors of Txnip-deficient mice. The upregulation of p53 preceded tumor development; however, bromodeoxyuridine (BrdU) labeling of normal hepatic tissue of Txnip-deficient mice did not reveal increased cell proliferation. Finally, microarray analyses of tumor, non-tumor adjacent, and normal tissue of Txnip-deficient mice highlighted the genetic differences leading to the predisposition and onset of HCC. Our findings suggest that Txnip deficiency is sufficient to initiate HCC and suggest novel mechanisms in hepatocarcinogenesis.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16607285   Authors: Sheth SS,Bodnar JS,Ghazalpour A,Thipphavong CK,Tsutsumi S,Tward AD,Demant P,Kodama T,Aburatani H,Lusis AJ
Exact source Table 5S
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(show 48 gene sets from the same authors)
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Organism Mus musculus
Contributed by Leona Saunders (MSigDB Team)
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Version history 3.1: First introduced

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