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

M. S. Kim, X. Chang, J. K. Nagpal, K. Yamashita, J. H. Baek, S. Dasgupta, G. Wu, M. Osada, J. H. Woo, W. H. Westra, B. Trink, E. A. Ratovitski, C. Moon, David Sidransky

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2045-2054
Number of pages10
JournalOncogene
Volume27
Issue number14
DOIs
StatePublished - Mar 27 2008

Fingerprint

N-Methyl-D-Aspartate Receptors
Colorectal Neoplasms
Growth
decitabine
Methylation
Colon
Epithelium
Cell Line
Neurotransmitter Receptor
Tumor Cell Line
Colonic Neoplasms
Neoplasms
Mucous Membrane
Apoptosis
Polymerase Chain Reaction
Brain
hydrogen sulfite

Keywords

  • 5-aza-2′- deoxycytidine
  • Biomarker
  • Colon cancer
  • NMDAR2A
  • Promoter hypermethylation
  • Tumor suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

The N-methyl-D-aspartate receptor type 2A is frequently methylated in human colorectal carcinoma and suppresses cell growth. / Kim, M. S.; Chang, X.; Nagpal, J. K.; Yamashita, K.; Baek, J. H.; Dasgupta, S.; Wu, G.; Osada, M.; Woo, J. H.; Westra, W. H.; Trink, B.; Ratovitski, E. A.; Moon, C.; Sidransky, David.

In: Oncogene, Vol. 27, No. 14, 27.03.2008, p. 2045-2054.

Research output: Contribution to journalArticle

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 2008, 'The N-methyl-D-aspartate receptor type 2A is frequently methylated in human colorectal carcinoma and suppresses cell growth', Oncogene, vol. 27, no. 14, pp. 2045-2054. https://doi.org/10.1038/sj.onc.1210842
Kim, M. S. ; Chang, X. ; Nagpal, J. K. ; Yamashita, K. ; Baek, J. H. ; Dasgupta, S. ; Wu, G. ; Osada, M. ; Woo, J. H. ; Westra, W. H. ; Trink, B. ; Ratovitski, E. A. ; Moon, C. ; Sidransky, David. / The N-methyl-D-aspartate receptor type 2A is frequently methylated in human colorectal carcinoma and suppresses cell growth. In: Oncogene. 2008 ; Vol. 27, No. 14. pp. 2045-2054.
@article{832aaaf8c0424beaaa97ca49cd70dc6f,
title = "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.",
keywords = "5-aza-2′- deoxycytidine, Biomarker, Colon cancer, NMDAR2A, Promoter hypermethylation, Tumor suppressor",
author = "Kim, {M. S.} and X. Chang and Nagpal, {J. K.} and K. Yamashita and Baek, {J. H.} and S. Dasgupta and G. Wu and M. Osada and Woo, {J. H.} and Westra, {W. H.} and B. Trink and Ratovitski, {E. A.} and C. Moon and David Sidransky",
year = "2008",
month = "3",
day = "27",
doi = "10.1038/sj.onc.1210842",
language = "English (US)",
volume = "27",
pages = "2045--2054",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "14",

}

TY - JOUR

T1 - The N-methyl-D-aspartate receptor type 2A is frequently methylated in human colorectal carcinoma and suppresses cell growth

AU - Kim, M. S.

AU - Chang, X.

AU - Nagpal, J. K.

AU - Yamashita, K.

AU - Baek, J. H.

AU - Dasgupta, S.

AU - Wu, G.

AU - Osada, M.

AU - Woo, J. H.

AU - Westra, W. H.

AU - Trink, B.

AU - Ratovitski, E. A.

AU - Moon, C.

AU - Sidransky, David

PY - 2008/3/27

Y1 - 2008/3/27

N2 - 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.

AB - 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.

KW - 5-aza-2′- deoxycytidine

KW - Biomarker

KW - Colon cancer

KW - NMDAR2A

KW - Promoter hypermethylation

KW - Tumor suppressor

UR - http://www.scopus.com/inward/record.url?scp=41149091772&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41149091772&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1210842

DO - 10.1038/sj.onc.1210842

M3 - Article

C2 - 17922030

AN - SCOPUS:41149091772

VL - 27

SP - 2045

EP - 2054

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 14

ER -