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

共 70 条

[1] Tumour class prediction and discovery by microarray-based DNA methylation analysis -: art. no. e21
Adorján, P
Distler, J
Lipscher, E
Model, F
Müller, J
Pelet, C
Braun, A
Florl, AR
Gütig, D
Grabs, G
Howe, A
Kursar, M
Lesche, R
Leu, E
Lewin, A
Maier, S
Müller, V
Otto, T
Scholz, C
Schulz, WA
Seifert, HH
Schwope, I
Ziebarth, H
Berlin, K
Piepenbrock, C
Olek, A
[J]. NUCLEIC ACIDS RESEARCH, 2002, 30 (05) : e21
[2] Aberrant patterns of DNA methylation, chromatin formation and gene expression in cancer
Baylin, SB
Esteller, M
Rountree, MR
Bachman, KE
Schuebel, K
Herman, JG
[J]. HUMAN MOLECULAR GENETICS, 2001, 10 (07) : 687 - 692
[3] CPG-RICH ISLANDS AND THE FUNCTION OF DNA METHYLATION
BIRD, AP
[J]. NATURE, 1986, 321 (6067) : 209 - 213
[4] Stat3 as an oncogene
Bromberg, JF
Wrzeszczynska, MH
Devgan, G
Zhao, YX
Pestell, RG
Albanese, C
Darnell, JE
[J]. CELL, 1999, 98 (03) : 295 - 303
[5] Down-regulation of T1A12/mac25, a novel insulin-like growth factor binding protein related gene, is associated with disease progression in breast carcinomas
Burger, AM
Zhang, X
Li, H
Ostrowski, JL
Beatty, B
Venanzoni, M
Papas, T
Seth, A
[J]. ONCOGENE, 1998, 16 (19) : 2459 - 2467
[6] Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer
Cameron, EE
Bachman, KE
Myöhänen, S
Herman, JG
Baylin, SB
[J]. NATURE GENETICS, 1999, 21 (01) : 103 - 107
[7] CHEN KK, 1995, INT J CANCER, P820
[8] INTERLEUKIN-1 TYPE-II RECEPTOR - A DECOY TARGET FOR IL-1 THAT IS REGULATED BY IL-4
COLOTTA, F
RE, F
MUZIO, M
BERTINI, R
POLENTARUTTI, N
SIRONI, M
GIRI, JG
DOWER, SK
SIMS, JE
MANTOVANI, A
[J]. SCIENCE, 1993, 261 (5120) : 472 - 475
[9] CREUSOT F, 1982, J BIOL CHEM, V257, P2041
[10] Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3
Dammann, R
Li, C
Yoon, JH
Chin, PL
Bates, S
Pfeifer, GP
[J]. NATURE GENETICS, 2000, 25 (03) : 315 - 319

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