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The N-methyl-D-aspartate receptor type 2A is frequently methylated in human colorectal carcinoma and suppresses cell growth.

Abstract：

:N-methyl-D-aspartate receptors (NMDARs) are the predominant excitatory neurotransmitter receptors in the mammalian brain. We found that among the three NMDARs examined (NMDAR1, NMDAR2A, NMDAR2B), only NMDAR2A was silenced in colorectal carcinoma (CRC) cell lines at basal line and reactivated by the demethylating agent, 5-aza-2'-deoxycytidine. NMDAR2A was expressed in normal colon epithelium, while expression was hardly detectable in colon cancer tissues. Promoter methylation of NMDAR2A was confirmed by bisulfite sequencing and combined bisulfite restriction analysis in the CRC cell lines and primary tumors. Quantitative methylation-specific PCR demonstrated NMDAR2A promoter hypermethylation in 82 of 100 primary human CRC, 15 of 100 normal corresponding epithelial tissues and 1 of 11 (9%) normal colon mucosa samples obtained from patients without cancer. Moreover, forced expression of full-length NMDAR2A in CRC cell lines induced apoptosis and almost abolished the ability of the cells to form colonies in culture, while NMDAR2A knockdown increased cell growth. Thus, NMDAR2A is commonly hypermethylated in primary human CRC and possesses tumor-suppressive activity.

journal_name

Oncogene

journal_title

Oncogene

authors

Kim MS,Chang X,Nagpal JK,Yamashita K,Baek JH,Dasgupta S,Wu G,Osada M,Woo JH,Westra WH,Trink B,Ratovitski EA,Moon C,Sidransky D

doi

10.1038/sj.onc.1210842

subject

Has Abstract

pub_date

2008-03-27 00:00:00

pages

2045-54

issue

14

eissn

0950-9232

issn

1476-5594

pii

1210842

journal_volume

27

pub_type

杂志文章

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