Gene Set: FUJIWARA_PARK2_IN_LIVER_CANCER_UP

Standard name FUJIWARA_PARK2_IN_LIVER_CANCER_UP
Systematic name M1343
Brief description Genes up-regulated in tumorous liver tissues from PARK2 [GeneID=5071] knockout mice compared to the normal, non-tumorous tissue from wild type mice.
Full description or abstract The parkin was first identified as a gene implicated in autosomal recessive juvenile Parkinsonism. Deregulation of the parkin gene, however, has been observed in various human cancers, suggesting that the parkin gene may be important in tumorigenesis. To gain insight into the physiologic role of parkin, we generated parkin-/- mice lacking exon 3 of the parkin gene. We demonstrated here that parkin-/- mice had enhanced hepatocyte proliferation and developed macroscopic hepatic tumors with the characteristics of hepatocellular carcinoma. Microarray analyses revealed that parkin deficiency caused the alteration of gene expression profiles in the liver. Among them, endogenous follistatin is commonly upregulated in both nontumorous and tumorous liver tissues of parkin-deficient mice. Parkin deficiency resulted in suppression of caspase activation and rendered hepatocytes resistant to apoptosis in a follistatin-dependent manner. These results suggested that parkin deficiency caused enhanced hepatocyte proliferation and resistance to apoptosis, resulting in hepatic tumor development, partially through the upregulation of endogenous follistatin. The finding that parkin-deficient mice are susceptible to hepatocarcinogenesis provided the first evidence showing that parkin is indeed a tumor suppressor gene.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18574468   Authors: Fujiwara M,Marusawa H,Wang HQ,Iwai A,Ikeuchi K,Imai Y,Kataoka A,Nukina N,Takahashi R,Chiba T
Exact source Table S1
Related gene sets (show 3 additional gene sets from the source publication)

(show 93 gene sets from the same authors)
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Organism Mus musculus
Contributed by Jessica Robertson (MSigDB Team)
Source platform Mouse_RefSeq
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Version history 3.1: First introduced

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