Systematic name M1399
Brief description Retinoic acid-responsive genes up-regulated in hepatocellular carcinoma (HCC) samples of TRIM24 [GeneID=8805] knockout mice.
Full description or abstract Hepatocellular carcinoma (HCC) is a major cause of death worldwide. Here, we provide evidence that the ligand-dependent nuclear receptor co-regulator Trim24 (also known as Tif1alpha) functions in mice as a liver-specific tumor suppressor. In Trim24-null mice, hepatocytes fail to execute proper cell cycle withdrawal during the neonatal-to-adult transition and continue to cycle in adult livers, becoming prone to a continuum of cellular alterations that progress toward metastatic HCC. Using pharmacological approaches, we show that inhibition of retinoic acid signaling markedly reduces hepatocyte proliferation in Trim24-/- mice. We further show that deletion of a single retinoic acid receptor alpha (Rara) allele in a Trim24-null background suppresses HCC development and restores wild-type expression of retinoic acid-responsive genes in the liver, thus demonstrating that in this genetic background Rara expresses an oncogenic activity correlating with a dysregulation of the retinoic acid signaling pathway. Our results not only provide genetic evidence that Trim24 and Rara co-regulate hepatocarcinogenesis in an antagonistic manner but also suggest that aberrant activation of Rara is deleterious to liver homeostasis.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18026104   Authors: Khetchoumian K,Teletin M,Tisserand J,Mark M,Herquel B,Ignat M,Zucman-Rossi J,Cammas F,Lerouge T,Thibault C,Metzger D,Chambon P,Losson R
Exact source Table 2S: FC > 2
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(show 39 gene sets from the same authors)
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Organism Mus musculus
Contributed by Leona Saunders (MSigDB Team)
Source platform AFFY_Mouse430
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Version history 3.0: First introduced

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