Cargando…
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...
Autores principales: | , , , , , , |
---|---|
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 |
_version_ | 1782396893232365568 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4618201 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT lindguroe adamts1crabp1andnr3c1identifiedasepigeneticallyderegulatedgenesincolorectaltumorigenesis AT kleivikristine adamts1crabp1andnr3c1identifiedasepigeneticallyderegulatedgenesincolorectaltumorigenesis AT melinggunni adamts1crabp1andnr3c1identifiedasepigeneticallyderegulatedgenesincolorectaltumorigenesis AT teixeiramanuelr adamts1crabp1andnr3c1identifiedasepigeneticallyderegulatedgenesincolorectaltumorigenesis AT thiisevensenespen adamts1crabp1andnr3c1identifiedasepigeneticallyderegulatedgenesincolorectaltumorigenesis AT rognumtorleivo adamts1crabp1andnr3c1identifiedasepigeneticallyderegulatedgenesincolorectaltumorigenesis AT lotheragnhilda adamts1crabp1andnr3c1identifiedasepigeneticallyderegulatedgenesincolorectaltumorigenesis |