Hypomethylation of the MN/CA9 promoter and upregulated MN/CA9 expression in human renal cell carcinoma

MN/CA9 is a cancer-related gene, frequently activated in human renal cell carcinomas (RCCs). To reveal the activation mechanism, we investigated the relationship between methylation status of the MN/CA9 promoter region and gene expression using 13 human RCCs, and examined the effect of in vitro CpG...

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Autores principales: Cho, M, Uemura, H, Kim, S-C, Kawada, Y, Yoshida, K, Hirao, Y, Konishi, N, Saga, S, Yoshikawa, K
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2001
Materias:
Regular Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364093/
https://www.ncbi.nlm.nih.gov/pubmed/11506497
http://dx.doi.org/10.1054/bjoc.2001.1951
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author Cho, M
Uemura, H
Kim, S-C
Kawada, Y
Yoshida, K
Hirao, Y
Konishi, N
Saga, S
Yoshikawa, K
author_facet Cho, M
Uemura, H
Kim, S-C
Kawada, Y
Yoshida, K
Hirao, Y
Konishi, N
Saga, S
Yoshikawa, K
author_sort Cho, M
collection PubMed
description MN/CA9 is a cancer-related gene, frequently activated in human renal cell carcinomas (RCCs). To reveal the activation mechanism, we investigated the relationship between methylation status of the MN/CA9 promoter region and gene expression using 13 human RCCs, and examined the effect of in vitro CpG methylation on the MN/CA9 promoter activity using a human RCC cell line (SK-RC-44), expressing MN/CA9. MN/CA9 expression was evaluated by RT-PCR and observed in 10 of 13 RCCs (77%). A total of 9 out of 10 MN/CA9-positive RCCs (90%) contained clear cell components. Methylation status of 6 CpGs in the MN/CA9 promoter region was decided by using the bisulfite genomic sequencing protocol. Out of 13 RCCs 9 (69%) showed partial hypomethylation of the CpG at −74 bp, while the other 4 RCCs and 3 normal kidney tissue samples showed complete methylation. Hypomethylation of the CpG at −74 bp was strongly correlated with MN/CA9 expression. Luciferase assay revealed that the MN/CA9 promoter activity was strongly suppressed by methylation of the CpG at −74 bp. These findings suggest that hypomethylation of the CpG at −74 bp in the MN/CA9 promoter region might play an important role in this gene activation of human RCC. © 2001 Cancer Research Campaign http://www.bjcancer.com
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spelling pubmed-23640932009-09-10 Hypomethylation of the MN/CA9 promoter and upregulated MN/CA9 expression in human renal cell carcinoma Cho, M Uemura, H Kim, S-C Kawada, Y Yoshida, K Hirao, Y Konishi, N Saga, S Yoshikawa, K Br J Cancer Regular Article MN/CA9 is a cancer-related gene, frequently activated in human renal cell carcinomas (RCCs). To reveal the activation mechanism, we investigated the relationship between methylation status of the MN/CA9 promoter region and gene expression using 13 human RCCs, and examined the effect of in vitro CpG methylation on the MN/CA9 promoter activity using a human RCC cell line (SK-RC-44), expressing MN/CA9. MN/CA9 expression was evaluated by RT-PCR and observed in 10 of 13 RCCs (77%). A total of 9 out of 10 MN/CA9-positive RCCs (90%) contained clear cell components. Methylation status of 6 CpGs in the MN/CA9 promoter region was decided by using the bisulfite genomic sequencing protocol. Out of 13 RCCs 9 (69%) showed partial hypomethylation of the CpG at −74 bp, while the other 4 RCCs and 3 normal kidney tissue samples showed complete methylation. Hypomethylation of the CpG at −74 bp was strongly correlated with MN/CA9 expression. Luciferase assay revealed that the MN/CA9 promoter activity was strongly suppressed by methylation of the CpG at −74 bp. These findings suggest that hypomethylation of the CpG at −74 bp in the MN/CA9 promoter region might play an important role in this gene activation of human RCC. © 2001 Cancer Research Campaign http://www.bjcancer.com Nature Publishing Group 2001-08 /pmc/articles/PMC2364093/ /pubmed/11506497 http://dx.doi.org/10.1054/bjoc.2001.1951 Text en Copyright © 2001 Cancer Research Campaign https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Regular Article
Cho, M
Uemura, H
Kim, S-C
Kawada, Y
Yoshida, K
Hirao, Y
Konishi, N
Saga, S
Yoshikawa, K
Hypomethylation of the MN/CA9 promoter and upregulated MN/CA9 expression in human renal cell carcinoma
title Hypomethylation of the MN/CA9 promoter and upregulated MN/CA9 expression in human renal cell carcinoma
title_full Hypomethylation of the MN/CA9 promoter and upregulated MN/CA9 expression in human renal cell carcinoma
title_fullStr Hypomethylation of the MN/CA9 promoter and upregulated MN/CA9 expression in human renal cell carcinoma
title_full_unstemmed Hypomethylation of the MN/CA9 promoter and upregulated MN/CA9 expression in human renal cell carcinoma
title_short Hypomethylation of the MN/CA9 promoter and upregulated MN/CA9 expression in human renal cell carcinoma
title_sort hypomethylation of the mn/ca9 promoter and upregulated mn/ca9 expression in human renal cell carcinoma
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364093/
https://www.ncbi.nlm.nih.gov/pubmed/11506497
http://dx.doi.org/10.1054/bjoc.2001.1951
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