Pharmacologic unmasking of epigenetically silenced tumor suppressor genes in esophageal squamous cell carcinoma

Keishi Yamashita, Sunil Upadhyay, Motonobu Osada, Mohammad O. Hoque, Yan Xiao, Masaki Mori, Fumiaki Sato, Stephen J. Meltzer, David Sidransky

Research output: Contribution to journalArticle

274 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)485-495
Number of pages11
JournalCancer Cell
Volume2
Issue number6
DOIs
Publication statusPublished - Dec 2002

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cell Biology
  • Cancer Research

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    Yamashita, K., Upadhyay, S., Osada, M., Hoque, M. O., Xiao, Y., Mori, M., Sato, F., Meltzer, S. J., & Sidransky, D. (2002). Pharmacologic unmasking of epigenetically silenced tumor suppressor genes in esophageal squamous cell carcinoma. Cancer Cell, 2(6), 485-495. https://doi.org/10.1016/S1535-6108(02)00215-5