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ADAMTS1, CRABP1, and NR3C1 Identified as Epigenetically Deregulated Genes in Colorectal Tumorigenesis

Background: Gene silencing through CpG island hypermethylation is a major mechanism in cancer development. In the present study, we aimed to identify and validate novel target genes inactivated through promoter hypermethylation in colorectal tumor development. Methods: With the use of microarrays, t...

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Autores principales: Lind, Guro E., Kleivi, Kristine, Meling, Gunn I., Teixeira, Manuel R., Thiis-Evensen, Espen, Rognum, Torleiv O., Lothe, Ragnhild A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: IOS Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618201/
https://www.ncbi.nlm.nih.gov/pubmed/17167179
http://dx.doi.org/10.1155/2006/949506
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author Lind, Guro E.
Kleivi, Kristine
Meling, Gunn I.
Teixeira, Manuel R.
Thiis-Evensen, Espen
Rognum, Torleiv O.
Lothe, Ragnhild A.
author_facet Lind, Guro E.
Kleivi, Kristine
Meling, Gunn I.
Teixeira, Manuel R.
Thiis-Evensen, Espen
Rognum, Torleiv O.
Lothe, Ragnhild A.
author_sort Lind, Guro E.
collection PubMed
description Background: Gene silencing through CpG island hypermethylation is a major mechanism in cancer development. In the present study, we aimed to identify and validate novel target genes inactivated through promoter hypermethylation in colorectal tumor development. Methods: With the use of microarrays, the gene expression profiles of colon cancer cell lines before and after treatment with the demethylating agent 5-aza-2′-deoxycytidine were identified and compared. The expression of the responding genes was compared with microarray expression data of primary colorectal carcinomas. Four of these down-regulated genes were subjected to methylation-specific PCR, bisulphite sequencing, and quantitative gene expression analysis using tumors (n=198), normal tissues (n=44), and cell lines (n=30). Results: Twenty-one genes with a CpG island in their promoter responded to treatment in cell lines, and were simultaneously down-regulated in primary colorectal carcinomas. Among 20 colon cancer cell lines, hypermethylation was subsequently identified for three of four analyzed genes, ADAMTS1 (85%), CRABP1 (90%), and NR3C1 (35%). For the latter two genes, hypermethylation was significantly associated with absence or reduced gene expression. The methylation status of ADAMTS1, CRABP1, and NR3C1 was further investigated in 116 colorectal carcinomas and adenomas. Twenty-three of 63 (37%), 7/60 (12%), and 2/63 (3%) adenomas, as well as 37/52 (71%), 25/51 (49%), and 13/51 (25%) carcinomas were hypermethylated for the respective genes. These genes were unmethylated in tumors (n=82) from three other organs, prostate, testis, and kidney. Finally, analysis of normal colorectal mucosa demonstrated that the observed promoter hypermethylation was cancer-specific. Conclusion: By using a refined microarray screening approach we present three genes with cancer-specific hypermethylation in colorectal tumors, ADAMTS1, CRABP1, and NR3C1.
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spelling pubmed-46182012016-01-12 ADAMTS1, CRABP1, and NR3C1 Identified as Epigenetically Deregulated Genes in Colorectal Tumorigenesis Lind, Guro E. Kleivi, Kristine Meling, Gunn I. Teixeira, Manuel R. Thiis-Evensen, Espen Rognum, Torleiv O. Lothe, Ragnhild A. Cell Oncol Other Background: Gene silencing through CpG island hypermethylation is a major mechanism in cancer development. In the present study, we aimed to identify and validate novel target genes inactivated through promoter hypermethylation in colorectal tumor development. Methods: With the use of microarrays, the gene expression profiles of colon cancer cell lines before and after treatment with the demethylating agent 5-aza-2′-deoxycytidine were identified and compared. The expression of the responding genes was compared with microarray expression data of primary colorectal carcinomas. Four of these down-regulated genes were subjected to methylation-specific PCR, bisulphite sequencing, and quantitative gene expression analysis using tumors (n=198), normal tissues (n=44), and cell lines (n=30). Results: Twenty-one genes with a CpG island in their promoter responded to treatment in cell lines, and were simultaneously down-regulated in primary colorectal carcinomas. Among 20 colon cancer cell lines, hypermethylation was subsequently identified for three of four analyzed genes, ADAMTS1 (85%), CRABP1 (90%), and NR3C1 (35%). For the latter two genes, hypermethylation was significantly associated with absence or reduced gene expression. The methylation status of ADAMTS1, CRABP1, and NR3C1 was further investigated in 116 colorectal carcinomas and adenomas. Twenty-three of 63 (37%), 7/60 (12%), and 2/63 (3%) adenomas, as well as 37/52 (71%), 25/51 (49%), and 13/51 (25%) carcinomas were hypermethylated for the respective genes. These genes were unmethylated in tumors (n=82) from three other organs, prostate, testis, and kidney. Finally, analysis of normal colorectal mucosa demonstrated that the observed promoter hypermethylation was cancer-specific. Conclusion: By using a refined microarray screening approach we present three genes with cancer-specific hypermethylation in colorectal tumors, ADAMTS1, CRABP1, and NR3C1. IOS Press 2006 2006-12-12 /pmc/articles/PMC4618201/ /pubmed/17167179 http://dx.doi.org/10.1155/2006/949506 Text en Copyright © 2006 Hindawi Publishing Corporation and the authors.
spellingShingle Other
Lind, Guro E.
Kleivi, Kristine
Meling, Gunn I.
Teixeira, Manuel R.
Thiis-Evensen, Espen
Rognum, Torleiv O.
Lothe, Ragnhild A.
ADAMTS1, CRABP1, and NR3C1 Identified as Epigenetically Deregulated Genes in Colorectal Tumorigenesis
title ADAMTS1, CRABP1, and NR3C1 Identified as Epigenetically Deregulated Genes in Colorectal Tumorigenesis
title_full ADAMTS1, CRABP1, and NR3C1 Identified as Epigenetically Deregulated Genes in Colorectal Tumorigenesis
title_fullStr ADAMTS1, CRABP1, and NR3C1 Identified as Epigenetically Deregulated Genes in Colorectal Tumorigenesis
title_full_unstemmed ADAMTS1, CRABP1, and NR3C1 Identified as Epigenetically Deregulated Genes in Colorectal Tumorigenesis
title_short ADAMTS1, CRABP1, and NR3C1 Identified as Epigenetically Deregulated Genes in Colorectal Tumorigenesis
title_sort adamts1, crabp1, and nr3c1 identified as epigenetically deregulated genes in colorectal tumorigenesis
topic Other
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618201/
https://www.ncbi.nlm.nih.gov/pubmed/17167179
http://dx.doi.org/10.1155/2006/949506
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