HOXA5 Regulates hMLH1 Expression in Breast Cancer Cells
Homeobox protein HOXA5 functions as a transcriptional factor for genes that are not only involved in segmentation identity but also in cell differentiation. Although HOXA5 has been shown to regulate the expression of the tumor-suppressor protein p53, its role in breast tumorigenesis is not well unde...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2006-04-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558606800643 |
| _version_ | 1818564433121640448 |
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| author | Sai Duriseti Paul T. Winnard, Jr. Yelena Mironchik Farhad Vesuna Ana Raman Venu Raman |
| author_facet | Sai Duriseti Paul T. Winnard, Jr. Yelena Mironchik Farhad Vesuna Ana Raman Venu Raman |
| author_sort | Sai Duriseti |
| collection | DOAJ |
| description | Homeobox protein HOXA5 functions as a transcriptional factor for genes that are not only involved in segmentation identity but also in cell differentiation. Although HOXA5 has been shown to regulate the expression of the tumor-suppressor protein p53, its role in breast tumorigenesis is not well understood. Using yeast as a model system, we now demonstrate that overexpression of HOXA5 in yeast can be used to identify downstream target genes that are homologous in humans. One such identified gene was that of the mismatch repair pathway component Mutt homolog 1. Analysis of the promoter region of the gene for human Mutt homolog 1 (hMLH1) displayed several putative HOXA5-binding sites. In transient transfection experiments, the overexpression of HOXA5 transactivated the hMLH1 promoter-reporter construct. In addition, chromatin immunoprecipitation assay using a human breast cancer cell line MCF-7 demonstrated that HOXA5 binds to the hMLH1 promoter in vivo. Furthermore, we demonstrate that, in the presence of HOXA5, there is an increase in in vivo repair activity in MCF-7 cells. Taken together, our results indicate that HOXA5 is a transcriptional regulator of hMLH1 in breast cancer cells. |
| first_indexed | 2024-12-14T01:28:50Z |
| format | Article |
| id | doaj.art-8b479d20ab5c41c6b21127e5c983b133 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-14T01:28:50Z |
| publishDate | 2006-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-8b479d20ab5c41c6b21127e5c983b1332022-12-21T23:22:06ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022006-04-018425025810.1593/neo.05766HOXA5 Regulates hMLH1 Expression in Breast Cancer CellsSai Duriseti0Paul T. Winnard, Jr.1Yelena Mironchik2Farhad Vesuna3Ana Raman4Venu Raman5Department of Radiology, Johns Hopkins University School of Medicine, 340 Traylor Building, 720 Rutland Avenue, Baltimore, MD 21205, USADepartment of Radiology, Johns Hopkins University School of Medicine, 340 Traylor Building, 720 Rutland Avenue, Baltimore, MD 21205, USADepartment of Radiology, Johns Hopkins University School of Medicine, 340 Traylor Building, 720 Rutland Avenue, Baltimore, MD 21205, USADepartment of Radiology, Johns Hopkins University School of Medicine, 340 Traylor Building, 720 Rutland Avenue, Baltimore, MD 21205, USADepartment of Biological Sciences, University of Maryland at Baltimore County, Baltimore, MD 21250, USADepartment of Radiology, Johns Hopkins University School of Medicine, 340 Traylor Building, 720 Rutland Avenue, Baltimore, MD 21205, USAHomeobox protein HOXA5 functions as a transcriptional factor for genes that are not only involved in segmentation identity but also in cell differentiation. Although HOXA5 has been shown to regulate the expression of the tumor-suppressor protein p53, its role in breast tumorigenesis is not well understood. Using yeast as a model system, we now demonstrate that overexpression of HOXA5 in yeast can be used to identify downstream target genes that are homologous in humans. One such identified gene was that of the mismatch repair pathway component Mutt homolog 1. Analysis of the promoter region of the gene for human Mutt homolog 1 (hMLH1) displayed several putative HOXA5-binding sites. In transient transfection experiments, the overexpression of HOXA5 transactivated the hMLH1 promoter-reporter construct. In addition, chromatin immunoprecipitation assay using a human breast cancer cell line MCF-7 demonstrated that HOXA5 binds to the hMLH1 promoter in vivo. Furthermore, we demonstrate that, in the presence of HOXA5, there is an increase in in vivo repair activity in MCF-7 cells. Taken together, our results indicate that HOXA5 is a transcriptional regulator of hMLH1 in breast cancer cells.http://www.sciencedirect.com/science/article/pii/S1476558606800643Breast cancermismatch repairhomeotic geneyeastpromoter analyses |
| spellingShingle | Sai Duriseti Paul T. Winnard, Jr. Yelena Mironchik Farhad Vesuna Ana Raman Venu Raman HOXA5 Regulates hMLH1 Expression in Breast Cancer Cells Neoplasia: An International Journal for Oncology Research Breast cancer mismatch repair homeotic gene yeast promoter analyses |
| title | HOXA5 Regulates hMLH1 Expression in Breast Cancer Cells |
| title_full | HOXA5 Regulates hMLH1 Expression in Breast Cancer Cells |
| title_fullStr | HOXA5 Regulates hMLH1 Expression in Breast Cancer Cells |
| title_full_unstemmed | HOXA5 Regulates hMLH1 Expression in Breast Cancer Cells |
| title_short | HOXA5 Regulates hMLH1 Expression in Breast Cancer Cells |
| title_sort | hoxa5 regulates hmlh1 expression in breast cancer cells |
| topic | Breast cancer mismatch repair homeotic gene yeast promoter analyses |
| url | http://www.sciencedirect.com/science/article/pii/S1476558606800643 |
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