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Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells

BACKGROUND: Activator protein 2 gamma (AP-2γ) is a member of the transcription factor activator protein-2 (AP-2) family, which is developmentally regulated and plays a role in human neoplasia. AP-2γ has been found to be overexpressed in most breast cancers, and have a dual role to inhibit tumor init...

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Autores principales: Ailan, He, Xiangwen, Xiao, Daolong, Ren, Lu, Gan, Xiaofeng, Ding, Xi, Qiao, Xingwang, Hu, Rushi, Liu, Jian, Zhang, Shuanglin, Xiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224728/
https://www.ncbi.nlm.nih.gov/pubmed/19671168
http://dx.doi.org/10.1186/1471-2407-9-279
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author Ailan, He
Xiangwen, Xiao
Daolong, Ren
Lu, Gan
Xiaofeng, Ding
Xi, Qiao
Xingwang, Hu
Rushi, Liu
Jian, Zhang
Shuanglin, Xiang
author_facet Ailan, He
Xiangwen, Xiao
Daolong, Ren
Lu, Gan
Xiaofeng, Ding
Xi, Qiao
Xingwang, Hu
Rushi, Liu
Jian, Zhang
Shuanglin, Xiang
author_sort Ailan, He
collection PubMed
description BACKGROUND: Activator protein 2 gamma (AP-2γ) is a member of the transcription factor activator protein-2 (AP-2) family, which is developmentally regulated and plays a role in human neoplasia. AP-2γ has been found to be overexpressed in most breast cancers, and have a dual role to inhibit tumor initiation and promote tumor progression afterwards during mammary tumorigensis. METHODS: To identify the gene targets that mediate its effects, we performed chromatin immunoprecipitation (ChIP) to isolate AP-2γ binding sites on genomic DNA from human breast cancer cell line MDA-MB-453. RESULTS: 20 novel DNA fragments proximal to potential AP-2γ targets were obtained. They are categorized into functional groups of carcinogenesis, metabolism and others. A combination of sequence analysis, reporter gene assays, quantitative real-time PCR, electrophoretic gel mobility shift assays and immunoblot analysis further confirmed the four AP-2γ target genes in carcinogenesis group: ErbB2, CDH2, HPSE and IGSF11. Our results were consistent with the previous reports that ErbB2 was the target gene of AP-2γ. Decreased expression and overexpression of AP-2γ in human breast cancer cells significantly altered the expression of these four genes, indicating that AP-2γ directly regulates them. CONCLUSION: This suggested that AP-2γ can coordinate the expression of a network of genes, involving in carcinogenesis, especially in breast cancer. They could serve as therapeutic targets against breast cancers in the future.
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spelling pubmed-32247282011-11-28 Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells Ailan, He Xiangwen, Xiao Daolong, Ren Lu, Gan Xiaofeng, Ding Xi, Qiao Xingwang, Hu Rushi, Liu Jian, Zhang Shuanglin, Xiang BMC Cancer Research Article BACKGROUND: Activator protein 2 gamma (AP-2γ) is a member of the transcription factor activator protein-2 (AP-2) family, which is developmentally regulated and plays a role in human neoplasia. AP-2γ has been found to be overexpressed in most breast cancers, and have a dual role to inhibit tumor initiation and promote tumor progression afterwards during mammary tumorigensis. METHODS: To identify the gene targets that mediate its effects, we performed chromatin immunoprecipitation (ChIP) to isolate AP-2γ binding sites on genomic DNA from human breast cancer cell line MDA-MB-453. RESULTS: 20 novel DNA fragments proximal to potential AP-2γ targets were obtained. They are categorized into functional groups of carcinogenesis, metabolism and others. A combination of sequence analysis, reporter gene assays, quantitative real-time PCR, electrophoretic gel mobility shift assays and immunoblot analysis further confirmed the four AP-2γ target genes in carcinogenesis group: ErbB2, CDH2, HPSE and IGSF11. Our results were consistent with the previous reports that ErbB2 was the target gene of AP-2γ. Decreased expression and overexpression of AP-2γ in human breast cancer cells significantly altered the expression of these four genes, indicating that AP-2γ directly regulates them. CONCLUSION: This suggested that AP-2γ can coordinate the expression of a network of genes, involving in carcinogenesis, especially in breast cancer. They could serve as therapeutic targets against breast cancers in the future. BioMed Central 2009-08-11 /pmc/articles/PMC3224728/ /pubmed/19671168 http://dx.doi.org/10.1186/1471-2407-9-279 Text en Copyright ©2009 Ailan 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
Ailan, He
Xiangwen, Xiao
Daolong, Ren
Lu, Gan
Xiaofeng, Ding
Xi, Qiao
Xingwang, Hu
Rushi, Liu
Jian, Zhang
Shuanglin, Xiang
Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells
title Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells
title_full Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells
title_fullStr Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells
title_full_unstemmed Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells
title_short Identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells
title_sort identification of target genes of transcription factor activator protein 2 gamma in breast cancer cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224728/
https://www.ncbi.nlm.nih.gov/pubmed/19671168
http://dx.doi.org/10.1186/1471-2407-9-279
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