Systematic name M16701
Brief description Genes down-regulated in H358 cells (lung cancer) by inducible expression of FOXA2 [GeneID=3170] in a Tet-off system.
Full description or abstract The forkhead transcription factor hepatocyte nuclear factor 3beta (HNF3beta) is essential in foregut development and the regulation of lung-specific genes. HNF3beta expression leads to growth arrest and apoptosis in lung cancer cells and HNF3beta is a candidate tumor suppressor in lung cancer. In a transcriptional profiling study using a conditional cell line system, we now identify 15-PGDH as one of the major genes induced by HNF3beta expression. 15-PGDH is a critical metabolic enzyme of proliferative prostaglandins, an antagonist to cyclooxygenase-2 and a tumor suppressor in colon cancer. We confirmed the regulation of 15-PGDH expression by HNF3beta in a number of systems and showed direct binding of HNF3beta to 15-PGDH promoter elements. Western blotting of lung cancer cell lines and immunohistochemical examination of human lung cancer tissues found loss of 15-PGDH expression in approximately 65% of lung cancers. Further studies using in vitro cell-based assays and in vivo xenograft tumorigenesis assays showed a lack of in vitro but significant in vivo tumor suppressor activity of 15-PGDH via an antiangiogenic mechanism analogous to its role in colon cancer. In summary, we identify 15-PGDH as a direct downstream effector of HNF3beta and show that 15-PGDH acts as a tumor suppressor in lung cancer.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18593902   Authors: Huang G,Eisenberg R,Yan M,Monti S,Lawrence E,Fu P,Walbroehl J,L÷wenberg E,Golub T,Merchan J,Tenen DG,Markowitz SD,Halmos B
Exact source Table 2S
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(show 20 gene sets from the same authors)
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Organism Homo sapiens
Contributed by Leona Saunders (MSigDB Team)
Source platform AFFY_HG_U133
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Version history 3.0: First introduced

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