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Chromodomain helicase DNA binding protein 5 plays a tumor suppressor role in human breast cancer
INTRODUCTION: The chromodomain helicase DNA binding protein 5 (CHD5) has recently been identified as a tumor suppressor in a mouse model. The CHD5 locus at 1p36 is deleted, and its mutation has been detected in breast cancer. We, therefore, evaluated whether CHD5 plays a role in human breast cancer....
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446335/ https://www.ncbi.nlm.nih.gov/pubmed/22569290 http://dx.doi.org/10.1186/bcr3182 |
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author | Wu, Xiao Zhu, Zhengmao Li, Weidong Fu, Xiaoying Su, Dan Fu, Liya Zhang, Zhiqian Luo, Ang Sun, Xiaodong Fu, Li Dong, Jin-Tang |
author_facet | Wu, Xiao Zhu, Zhengmao Li, Weidong Fu, Xiaoying Su, Dan Fu, Liya Zhang, Zhiqian Luo, Ang Sun, Xiaodong Fu, Li Dong, Jin-Tang |
author_sort | Wu, Xiao |
collection | PubMed |
description | INTRODUCTION: The chromodomain helicase DNA binding protein 5 (CHD5) has recently been identified as a tumor suppressor in a mouse model. The CHD5 locus at 1p36 is deleted, and its mutation has been detected in breast cancer. We, therefore, evaluated whether CHD5 plays a role in human breast cancer. METHODS: We screened mutations in 55 tumors, determined promoter methylation in 39 tumors, measured RNA expression in 90 tumors, analyzed protein expression in 289 tumors, and correlated expression changes with clinicopathological characteristics of breast cancer. Functional effects of CHD5 on cell proliferation, invasion and tumorigenesis were also tested. RESULTS: Although only one mutation was detected, CHD5 mRNA expression was significantly reduced, accompanied by frequent genomic deletion and promoter methylation, in breast cancer. The extent of methylation was significantly associated with reduced mRNA expression, and demethylating treatment restored CHD5 expression. Lower CHD5 mRNA levels correlated with lymph node metastasis (P = 0.026). CHD5 protein expression was also reduced in breast cancer, and lack of CHD5 expression significantly correlated with higher tumor stage, ER/PR-negativity, HER2 positivity, distant metastasis and worse patient survival (P ≤ 0.01). Functionally, ectopic expression of CHD5 in breast cancer cells inhibited cell proliferation and invasion in vitro and tumorigenesis in nude mice. Consistent with the inhibition of invasion, CHD5 down-regulated mesenchymal markers vimentin, N-cadherin and ZEB1 in breast cancer cells. CONCLUSION: Down-regulation of CHD5, mediated at least in part by promoter methylation, contributes to the development and progression of human breast cancer. |
format | Online Article Text |
id | pubmed-3446335 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-34463352012-09-20 Chromodomain helicase DNA binding protein 5 plays a tumor suppressor role in human breast cancer Wu, Xiao Zhu, Zhengmao Li, Weidong Fu, Xiaoying Su, Dan Fu, Liya Zhang, Zhiqian Luo, Ang Sun, Xiaodong Fu, Li Dong, Jin-Tang Breast Cancer Res Research Article INTRODUCTION: The chromodomain helicase DNA binding protein 5 (CHD5) has recently been identified as a tumor suppressor in a mouse model. The CHD5 locus at 1p36 is deleted, and its mutation has been detected in breast cancer. We, therefore, evaluated whether CHD5 plays a role in human breast cancer. METHODS: We screened mutations in 55 tumors, determined promoter methylation in 39 tumors, measured RNA expression in 90 tumors, analyzed protein expression in 289 tumors, and correlated expression changes with clinicopathological characteristics of breast cancer. Functional effects of CHD5 on cell proliferation, invasion and tumorigenesis were also tested. RESULTS: Although only one mutation was detected, CHD5 mRNA expression was significantly reduced, accompanied by frequent genomic deletion and promoter methylation, in breast cancer. The extent of methylation was significantly associated with reduced mRNA expression, and demethylating treatment restored CHD5 expression. Lower CHD5 mRNA levels correlated with lymph node metastasis (P = 0.026). CHD5 protein expression was also reduced in breast cancer, and lack of CHD5 expression significantly correlated with higher tumor stage, ER/PR-negativity, HER2 positivity, distant metastasis and worse patient survival (P ≤ 0.01). Functionally, ectopic expression of CHD5 in breast cancer cells inhibited cell proliferation and invasion in vitro and tumorigenesis in nude mice. Consistent with the inhibition of invasion, CHD5 down-regulated mesenchymal markers vimentin, N-cadherin and ZEB1 in breast cancer cells. CONCLUSION: Down-regulation of CHD5, mediated at least in part by promoter methylation, contributes to the development and progression of human breast cancer. BioMed Central 2012 2012-05-08 /pmc/articles/PMC3446335/ /pubmed/22569290 http://dx.doi.org/10.1186/bcr3182 Text en Copyright ©2012 Wu 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 Wu, Xiao Zhu, Zhengmao Li, Weidong Fu, Xiaoying Su, Dan Fu, Liya Zhang, Zhiqian Luo, Ang Sun, Xiaodong Fu, Li Dong, Jin-Tang Chromodomain helicase DNA binding protein 5 plays a tumor suppressor role in human breast cancer |
title | Chromodomain helicase DNA binding protein 5 plays a tumor suppressor role in human breast cancer |
title_full | Chromodomain helicase DNA binding protein 5 plays a tumor suppressor role in human breast cancer |
title_fullStr | Chromodomain helicase DNA binding protein 5 plays a tumor suppressor role in human breast cancer |
title_full_unstemmed | Chromodomain helicase DNA binding protein 5 plays a tumor suppressor role in human breast cancer |
title_short | Chromodomain helicase DNA binding protein 5 plays a tumor suppressor role in human breast cancer |
title_sort | chromodomain helicase dna binding protein 5 plays a tumor suppressor role in human breast cancer |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446335/ https://www.ncbi.nlm.nih.gov/pubmed/22569290 http://dx.doi.org/10.1186/bcr3182 |
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