Human Gene Set: TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA


Standard name TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA
Systematic name M14455
Brief description Genes with hypermethylated DNA in all four esophageal squamous cell carcinoma (ESCC) lines analyzed.
Full description or abstract Epigenetic alterations and the resulting inactivation of tumor suppressor genes often contribute to the development of various cancers. To identify novel candidates that may be silenced by aberrant methylation in esophageal squamous-cell carcinoma (ESCC), we analysed ESCC cell lines by a recently developed method known as bacterial artificial chromosome array-based methylated CpG island amplification (BAMCA), and selected candidates through BAMCA-assisted strategy. In the course of this program, we identified frequent CpG methylation-dependent silencing of the gene encoding cellular retinoic acid binding protein 1 (CRABP1) in our panel of ESCC cell lines. Expression of CRABP1 mRNA was restored in gene-silenced ESCC cells after treatment with 5-aza 2'-deoxycytidine. The DNA methylation status of the CRABP1 CpG island with clear promoter activity correlated inversely with expression of this gene. CpG methylation of CRABP1 was frequently observed in primary ESCC tissues as well. Restoration of CRABP1 expression in ESCC cells lacking the protein reduced cell growth by inducing arrest at G(0)-G(1), whereas knockdown of the gene in cells expressing CRABP1 promoted cell growth. Among 113 primary ESCC tumors, the absence of immunoreactive CRABP1 was significantly associated with de-differentiation of cancer cells and with distant lymph-node metastases in the patients. These results indicate that CRABP1 appears to have a tumor-suppressor function in esophageal epithelium, and its epigenetic silencing may play a pivotal role during esophageal carcinogenesis. Its expression status in biopsies or resected tumors might serve as an index for identifying ESCC patients for whom combined therapeutic modalities would be recommended.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17438526   Authors: Tanaka K,Imoto I,Inoue J,Kozaki K,Tsuda H,Shimada Y,Aiko S,Yoshizumi Y,Iwai T,Kawano T,Inazawa J
Exact source Table 1S
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Source species Homo sapiens
Contributed by Arthur Liberzon (MSigDB Team)
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identifier namespace		 Human_NCBI_Gene_ID
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Version history 3.0: First introduced

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