Cargando…
ECRG4 is a candidate tumor suppressor gene frequently hypermethylated in colorectal carcinoma and glioma
BACKGROUND: Cancer cells display widespread changes in DNA methylation that may lead to genetic instability by global hypomethylation and aberrant silencing of tumor suppressor genes by focal hypermethylation. In turn, altered DNA methylation patterns have been used to identify putative tumor suppre...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2009
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804712/ https://www.ncbi.nlm.nih.gov/pubmed/20017917 http://dx.doi.org/10.1186/1471-2407-9-447 |
_version_ | 1782176180715126784 |
---|---|
author | Götze, Silke Feldhaus, Valeska Traska, Thilo Wolter, Marietta Reifenberger, Guido Tannapfel, Andrea Kuhnen, Cornelius Martin, Dirk Müller, Oliver Sievers, Sonja |
author_facet | Götze, Silke Feldhaus, Valeska Traska, Thilo Wolter, Marietta Reifenberger, Guido Tannapfel, Andrea Kuhnen, Cornelius Martin, Dirk Müller, Oliver Sievers, Sonja |
author_sort | Götze, Silke |
collection | PubMed |
description | BACKGROUND: Cancer cells display widespread changes in DNA methylation that may lead to genetic instability by global hypomethylation and aberrant silencing of tumor suppressor genes by focal hypermethylation. In turn, altered DNA methylation patterns have been used to identify putative tumor suppressor genes. METHODS: In a methylation screening approach, we identified ECRG4 as a differentially methylated gene. We analyzed different cancer cells for ECRG4 promoter methylation by COBRA and bisulfite sequencing. Gene expression analysis was carried out by semi-quantitative RT-PCR. The ECRG4 coding region was cloned and transfected into colorectal carcinoma cells. Cell growth was assessed by MTT and BrdU assays. ECRG4 localization was analyzed by fluorescence microscopy and Western blotting after transfection of an ECRG4-eGFP fusion gene. RESULTS: We found a high frequency of ECRG4 promoter methylation in various cancer cell lines. Remarkably, aberrant methylation of ECRG4 was also found in primary human tumor tissues, including samples from colorectal carcinoma and from malignant gliomas. ECRG4 hypermethylation associated strongly with transcriptional silencing and its expression could be re-activated in vitro by demethylating treatment with 5-aza-2'-deoxycytidine. Overexpression of ECRG4 in colorectal carcinoma cells led to a significant decrease in cell growth. In transfected cells, ECRG4 protein was detectable within the Golgi secretion machinery as well as in the culture medium. CONCLUSIONS: ECRG4 is silenced via promoter hypermethylation in different types of human cancer cells. Its gene product may act as inhibitor of cell proliferation in colorectal carcinoma cells and may play a role as extracellular signaling molecule. |
format | Text |
id | pubmed-2804712 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-28047122010-01-12 ECRG4 is a candidate tumor suppressor gene frequently hypermethylated in colorectal carcinoma and glioma Götze, Silke Feldhaus, Valeska Traska, Thilo Wolter, Marietta Reifenberger, Guido Tannapfel, Andrea Kuhnen, Cornelius Martin, Dirk Müller, Oliver Sievers, Sonja BMC Cancer Research Article BACKGROUND: Cancer cells display widespread changes in DNA methylation that may lead to genetic instability by global hypomethylation and aberrant silencing of tumor suppressor genes by focal hypermethylation. In turn, altered DNA methylation patterns have been used to identify putative tumor suppressor genes. METHODS: In a methylation screening approach, we identified ECRG4 as a differentially methylated gene. We analyzed different cancer cells for ECRG4 promoter methylation by COBRA and bisulfite sequencing. Gene expression analysis was carried out by semi-quantitative RT-PCR. The ECRG4 coding region was cloned and transfected into colorectal carcinoma cells. Cell growth was assessed by MTT and BrdU assays. ECRG4 localization was analyzed by fluorescence microscopy and Western blotting after transfection of an ECRG4-eGFP fusion gene. RESULTS: We found a high frequency of ECRG4 promoter methylation in various cancer cell lines. Remarkably, aberrant methylation of ECRG4 was also found in primary human tumor tissues, including samples from colorectal carcinoma and from malignant gliomas. ECRG4 hypermethylation associated strongly with transcriptional silencing and its expression could be re-activated in vitro by demethylating treatment with 5-aza-2'-deoxycytidine. Overexpression of ECRG4 in colorectal carcinoma cells led to a significant decrease in cell growth. In transfected cells, ECRG4 protein was detectable within the Golgi secretion machinery as well as in the culture medium. CONCLUSIONS: ECRG4 is silenced via promoter hypermethylation in different types of human cancer cells. Its gene product may act as inhibitor of cell proliferation in colorectal carcinoma cells and may play a role as extracellular signaling molecule. BioMed Central 2009-12-17 /pmc/articles/PMC2804712/ /pubmed/20017917 http://dx.doi.org/10.1186/1471-2407-9-447 Text en Copyright ©2009 Götze et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Götze, Silke Feldhaus, Valeska Traska, Thilo Wolter, Marietta Reifenberger, Guido Tannapfel, Andrea Kuhnen, Cornelius Martin, Dirk Müller, Oliver Sievers, Sonja ECRG4 is a candidate tumor suppressor gene frequently hypermethylated in colorectal carcinoma and glioma |
title | ECRG4 is a candidate tumor suppressor gene frequently hypermethylated in colorectal carcinoma and glioma |
title_full | ECRG4 is a candidate tumor suppressor gene frequently hypermethylated in colorectal carcinoma and glioma |
title_fullStr | ECRG4 is a candidate tumor suppressor gene frequently hypermethylated in colorectal carcinoma and glioma |
title_full_unstemmed | ECRG4 is a candidate tumor suppressor gene frequently hypermethylated in colorectal carcinoma and glioma |
title_short | ECRG4 is a candidate tumor suppressor gene frequently hypermethylated in colorectal carcinoma and glioma |
title_sort | ecrg4 is a candidate tumor suppressor gene frequently hypermethylated in colorectal carcinoma and glioma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804712/ https://www.ncbi.nlm.nih.gov/pubmed/20017917 http://dx.doi.org/10.1186/1471-2407-9-447 |
work_keys_str_mv | AT gotzesilke ecrg4isacandidatetumorsuppressorgenefrequentlyhypermethylatedincolorectalcarcinomaandglioma AT feldhausvaleska ecrg4isacandidatetumorsuppressorgenefrequentlyhypermethylatedincolorectalcarcinomaandglioma AT traskathilo ecrg4isacandidatetumorsuppressorgenefrequentlyhypermethylatedincolorectalcarcinomaandglioma AT woltermarietta ecrg4isacandidatetumorsuppressorgenefrequentlyhypermethylatedincolorectalcarcinomaandglioma AT reifenbergerguido ecrg4isacandidatetumorsuppressorgenefrequentlyhypermethylatedincolorectalcarcinomaandglioma AT tannapfelandrea ecrg4isacandidatetumorsuppressorgenefrequentlyhypermethylatedincolorectalcarcinomaandglioma AT kuhnencornelius ecrg4isacandidatetumorsuppressorgenefrequentlyhypermethylatedincolorectalcarcinomaandglioma AT martindirk ecrg4isacandidatetumorsuppressorgenefrequentlyhypermethylatedincolorectalcarcinomaandglioma AT mulleroliver ecrg4isacandidatetumorsuppressorgenefrequentlyhypermethylatedincolorectalcarcinomaandglioma AT sieverssonja ecrg4isacandidatetumorsuppressorgenefrequentlyhypermethylatedincolorectalcarcinomaandglioma |