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

被引：293

作者：

Yamashita, K

Upadhyay, S

Osada, M

Hoque, MO

Xiao, Y

Mori, M

Sato, F

Meltzer, SJ

Sidransky, D

机构：

[1] Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA

[2] Kyushu Univ, Inst Med, Dept Surg Oncol, Beppu, Oita 8740838, Japan

[3] Univ Maryland, Sch Med, Dept Med, Div Gastroenterol, Baltimore, MD 21201 USA

[4] Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA

[5] Baltimore VA Hosp, Baltimore, MD 21201 USA

来源：

CANCER CELL | 2002年 / 2卷 / 06期

关键词：

D O I：

10.1016/S1535-6108(02)00215-5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：485 / 495

页数：11

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