Author/Authors :
Yamashita، نويسنده , , Keishi and Upadhyay، نويسنده , , Sunil and Osada، نويسنده , , Motonobu and Hoque، نويسنده , , Mohammad O and Xiao، نويسنده , , Yan and Mori، نويسنده , , Masaki and Sato، نويسنده , , Fumiaki and Meltzer، نويسنده , , Stephen J and Sidransky، نويسنده , , David، نويسنده ,
Abstract :
We performed a comprehensive survey of commonly inactivated tumor suppressor genes in esophageal squamous cell carcinoma (ESCC) based on functional reactivation of epigenetically silenced tumor suppressor genes by 5-aza-2′-deoxycytidine and trichostatin A using microarrays containing 12599 genes. Among 58 genes identified by this approach, 44 (76%) harbored dense CpG islands in the promoter regions. Thirteen of twenty-two tested gene promoters were methylated in cell lines, and ten in primary ESCC accompanied by silencing at the mRNA level. Potent growth suppressive activity of three genes including CRIP-1, Apolipoprotein D, and Neuromedin U in ESCC cells was demonstrated by colony focus assays. Pharmacologic reversal of epigenetic silencing is a powerful approach for comprehensive identification of tumor suppressor genes in human cancers.
