STANDARD_NAME FUJIWARA_PARK2_IN_LIVER_CANCER_UP SYSTEMATIC_NAME M1343 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/FUJIWARA_PARK2_IN_LIVER_CANCER_UP NAMESPACE Mouse_RefSeq DESCRIPTION_BRIEF Genes up-regulated in tumorous liver tissues from PARK2 [GeneID=5071] knockout mice compared to the normal, non-tumorous tissue from wild type 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 S1 FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS NM_007423,NM_007468,NM_007527,NM_007633,NM_008046,NM_008146,NM_013749,NM_031167 GENE_SYMBOLS AFP,APOA4,BAX,CCNE1,FST,GOLGA3,TNFRSF12A,IL1RN FOUNDER_NAMES