Gene Set: JIANG_TIP30_TARGETS_UP

Standard name JIANG_TIP30_TARGETS_UP
Systematic name M12641
Brief description Up-regulated genes in HepG2 cells (liver cancer) overexpressing an oncogenic variant of tumor suppressor TIP30 [GeneID=10553] compared to its wild type form.
Full description or abstract TIP30 is a tumor suppressor whose expression is altered in human liver, prostate, lung, colon, and breast cancers. Mice lacking TIP30 spontaneously developed hepatocellular carcinomas (HCC) and other tumors at a higher incidence than wild-type mice. Somatic missense mutations in the TIP30 gene were identified in human HCC tissue specimens, which resulted in instability or abnormal cellular distribution of TIP30 protein in cells. Here, we show that TIP30 mutants are able to promote cell growth and invasion and inhibit cisplatin-induced apoptosis in the HCC cell line HepG2 negative for endogenous TIP30. Moreover, one of the TIP30 mutants can dramatically accelerate tumor formation in immunodeficient mice. Analysis of gene expression in HepG2 cells, ectopically expressing either wild-type TIP30 or mutant TIP30, by Affymetrix GeneChip array, real-time quantitative PCR, and Western blotting assays reveals that TIP30 mutants can alter expression of genes involved in the regulation of tumorigenesis. This includes up-regulation of expression of N-cadherin and c-MYC and down-regulation of expression of p53 and E-cadherin. N-cadherin knockdown with small interfering RNA in HepG2 cells expressing mutant TIP30 resulted in a profound reduction in cell viability. Taken together, our data indicate that somatic mutations in the TIP30 gene may abolish its native tumor-suppressor activity and gain oncogenic activities partially through up-regulation of N-cadherin, thereby potentiating the pathogenesis of HCC in patients.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17440068   Authors: Jiang C,Pecha J,Hoshino I,Ankrapp D,Xiao H
Exact source Table 1S: Fold change > 1.7
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Organism Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform HUMAN_SEQ_ACCESSION
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Version history 3.0: First introduced

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