STANDARD_NAME FUJIWARA_PARK2_HEPATOCYTE_PROLIFERATION_DN SYSTEMATIC_NAME M1342 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/FUJIWARA_PARK2_HEPATOCYTE_PROLIFERATION_DN NAMESPACE MOUSE_SEQ_ACCESSION DESCRIPTION_BRIEF Genes commonly down-regulated in both non-tumorous and tumorous liver tissues of PARK2 [GeneID=5071] knockout mice. DESCRIPTION_FULL 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. PMID 18574468 GEOID GSE9651 AUTHORS Fujiwara M,Marusawa H,Wang HQ,Iwai A,Ikeuchi K,Imai Y,Kataoka A,Nukina N,Takahashi R,Chiba T CONTRIBUTOR Jessica Robertson CONTRIBUTOR_ORG MSigDB Team EXACT_SOURCE Table 3S FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS L04961,NM_007804,NM_007822,NM_008030,NM_008963,NM_012006,NM_013459,NM_029662,NM_134246,NM_194054 GENE_SYMBOLS XIST,CUX2,,FMO3,PTGDS,ACOT1,CFD,MFSD2A,ACOT1,RTN4 FOUNDER_NAMES