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NDRG2 gene copy number is not altered in colorectal carcinoma

AIM: To investigate if the down-regulation of N-myc Downstream Regulated Gene 2 (NDRG2) expression in colorectal carcinoma (CRC) is due to loss of the NDRG2 allele(s). METHODS: The following were investigated in the human colorectal cancer cell lines DLD-1, LoVo and SW-480: NDRG2 mRNA expression lev...

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Autores principales: Lorentzen, Anders, Mitchelmore, Cathy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309715/
https://www.ncbi.nlm.nih.gov/pubmed/28246586
http://dx.doi.org/10.5306/wjco.v8.i1.67
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author Lorentzen, Anders
Mitchelmore, Cathy
author_facet Lorentzen, Anders
Mitchelmore, Cathy
author_sort Lorentzen, Anders
collection PubMed
description AIM: To investigate if the down-regulation of N-myc Downstream Regulated Gene 2 (NDRG2) expression in colorectal carcinoma (CRC) is due to loss of the NDRG2 allele(s). METHODS: The following were investigated in the human colorectal cancer cell lines DLD-1, LoVo and SW-480: NDRG2 mRNA expression levels using quantitative reverse transcription-polymerase chain reaction (qRT-PCR); interaction of the MYC gene-regulatory protein with the NDRG2 promoter using chromatin immunoprecipitation; and NDRG2 promoter methylation using bisulfite sequencing. Furthermore, we performed qPCR to analyse the copy numbers of NDRG2 and MYC genes in the above three cell lines, 8 normal colorectal tissue samples and 40 CRC tissue samples. RESULTS: As expected, NDRG2 mRNA levels were low in the three colorectal cancer cell lines, compared to normal colon. Endogenous MYC protein interacted with the NDRG2 core promoter in all three cell lines. In addition, the NDRG2 promoter was heavily methylated in these cell lines, suggesting an epigenetic regulatory mechanism. Unaltered gene copy numbers of NDRG2 were observed in the three cell lines. In the colorectal tissues, one normal and three CRC samples showed partial or complete loss of one NDRG2 allele. In contrast, the MYC gene was amplified in one cell line and in more than 40% of the CRC cases. CONCLUSION: Our study suggests that the reduction in NDRG2 expression observed in CRC is due to transcriptional repression by MYC and promoter methylation, and is not due to allelic loss.
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spelling pubmed-53097152017-02-28 NDRG2 gene copy number is not altered in colorectal carcinoma Lorentzen, Anders Mitchelmore, Cathy World J Clin Oncol Basic Study AIM: To investigate if the down-regulation of N-myc Downstream Regulated Gene 2 (NDRG2) expression in colorectal carcinoma (CRC) is due to loss of the NDRG2 allele(s). METHODS: The following were investigated in the human colorectal cancer cell lines DLD-1, LoVo and SW-480: NDRG2 mRNA expression levels using quantitative reverse transcription-polymerase chain reaction (qRT-PCR); interaction of the MYC gene-regulatory protein with the NDRG2 promoter using chromatin immunoprecipitation; and NDRG2 promoter methylation using bisulfite sequencing. Furthermore, we performed qPCR to analyse the copy numbers of NDRG2 and MYC genes in the above three cell lines, 8 normal colorectal tissue samples and 40 CRC tissue samples. RESULTS: As expected, NDRG2 mRNA levels were low in the three colorectal cancer cell lines, compared to normal colon. Endogenous MYC protein interacted with the NDRG2 core promoter in all three cell lines. In addition, the NDRG2 promoter was heavily methylated in these cell lines, suggesting an epigenetic regulatory mechanism. Unaltered gene copy numbers of NDRG2 were observed in the three cell lines. In the colorectal tissues, one normal and three CRC samples showed partial or complete loss of one NDRG2 allele. In contrast, the MYC gene was amplified in one cell line and in more than 40% of the CRC cases. CONCLUSION: Our study suggests that the reduction in NDRG2 expression observed in CRC is due to transcriptional repression by MYC and promoter methylation, and is not due to allelic loss. Baishideng Publishing Group Inc 2017-02-10 2017-02-10 /pmc/articles/PMC5309715/ /pubmed/28246586 http://dx.doi.org/10.5306/wjco.v8.i1.67 Text en ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Basic Study
Lorentzen, Anders
Mitchelmore, Cathy
NDRG2 gene copy number is not altered in colorectal carcinoma
title NDRG2 gene copy number is not altered in colorectal carcinoma
title_full NDRG2 gene copy number is not altered in colorectal carcinoma
title_fullStr NDRG2 gene copy number is not altered in colorectal carcinoma
title_full_unstemmed NDRG2 gene copy number is not altered in colorectal carcinoma
title_short NDRG2 gene copy number is not altered in colorectal carcinoma
title_sort ndrg2 gene copy number is not altered in colorectal carcinoma
topic Basic Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309715/
https://www.ncbi.nlm.nih.gov/pubmed/28246586
http://dx.doi.org/10.5306/wjco.v8.i1.67
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