Identification of the Cellular Function and a Novel Transcriptional Regulation of NDRG1 Under Normoxia and Hypoxia in MCF-7 Breast Cancer Cells
碩士 === 國立臺灣大學 === 生理學研究所 === 102 === N-myc downstream-regulated gene 1 (NDRG1) has been reported to regulate tumor progression in various cancers. In addition, it plays a critical role in tumor adaptation to fluctuation of oxygen concentrations. Previously, we showed that NDRG1 was strongly up-regul...
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ndltd-TW-102NTU051160052016-03-09T04:24:04Z http://ndltd.ncl.edu.tw/handle/83722722442952786789 Identification of the Cellular Function and a Novel Transcriptional Regulation of NDRG1 Under Normoxia and Hypoxia in MCF-7 Breast Cancer Cells 探討乳癌細胞株MCF-7在常氧與缺氧下NDRG1對細胞功能的影響與受到的新轉錄調控 Wei-Yung Huang 黃為雍 碩士 國立臺灣大學 生理學研究所 102 N-myc downstream-regulated gene 1 (NDRG1) has been reported to regulate tumor progression in various cancers. In addition, it plays a critical role in tumor adaptation to fluctuation of oxygen concentrations. Previously, we showed that NDRG1 was strongly up-regulated under hypoxia in a breast cancer cell line MCF-7, and predicted to contain binding sites for aryl hydrocarbon receptor (AHR) at its promoter. However, the regulatory mechanism of NDRG1 expression under hypoxia and its cellular function remained elusive. Therefore, the aims of this study were to elucidate whether AHR could modulate NDRG1 expression, and to investigate the functional roles of NDRG1 upon changes in oxygen concentrations. In hypoxia, immunofluorescence staining and chromatin immunoprecipitation assays showed that AHR translocated to nuclei and bound to NDRG1 promoter (-412 ~ -388 bp). Also, over-expression of AHR facilitated cell proliferation and migration via up-regulation of NDRG1, whereas shRNA knockdown of NDRG1 reduced cell growth and motility. On the other hand, over-expression of NDRG1 under normoxia suppressed cell proliferation and migration ability. Tumor growth on the nude mice was also inhibited in cells over-expressed with NDRG1. Clinically, NDRG1 was down-regulated in breast cancer cell lines and tumor tissues. In summary, these results showed a novel mechanism of NDRG1 regulated by AHR upon hypoxic stress, and highlighted the dynamic role of NDRG1 in regulating cell growth and migration capacity during oxygen fluctuation in breast cancer. 賴亮全 2014 學位論文 ; thesis 56 en_US |
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碩士 === 國立臺灣大學 === 生理學研究所 === 102 === N-myc downstream-regulated gene 1 (NDRG1) has been reported to regulate tumor progression in various cancers. In addition, it plays a critical role in tumor adaptation to fluctuation of oxygen concentrations. Previously, we showed that NDRG1 was strongly up-regulated under hypoxia in a breast cancer cell line MCF-7, and predicted to contain binding sites for aryl hydrocarbon receptor (AHR) at its promoter. However, the regulatory mechanism of NDRG1 expression under hypoxia and its cellular function remained elusive. Therefore, the aims of this study were to elucidate whether AHR could modulate NDRG1 expression, and to investigate the functional roles of NDRG1 upon changes in oxygen concentrations. In hypoxia, immunofluorescence staining and chromatin immunoprecipitation assays showed that AHR translocated to nuclei and bound to NDRG1 promoter (-412 ~ -388 bp). Also, over-expression of AHR facilitated cell proliferation and migration via up-regulation of NDRG1, whereas shRNA knockdown of NDRG1 reduced cell growth and motility. On the other hand, over-expression of NDRG1 under normoxia suppressed cell proliferation and migration ability. Tumor growth on the nude mice was also inhibited in cells over-expressed with NDRG1. Clinically, NDRG1 was down-regulated in breast cancer cell lines and tumor tissues. In summary, these results showed a novel mechanism of NDRG1 regulated by AHR upon hypoxic stress, and highlighted the dynamic role of NDRG1 in regulating cell growth and migration capacity during oxygen fluctuation in breast cancer.
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賴亮全 |
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賴亮全 Wei-Yung Huang 黃為雍 |
author |
Wei-Yung Huang 黃為雍 |
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Wei-Yung Huang 黃為雍 Identification of the Cellular Function and a Novel Transcriptional Regulation of NDRG1 Under Normoxia and Hypoxia in MCF-7 Breast Cancer Cells |
author_sort |
Wei-Yung Huang |
title |
Identification of the Cellular Function and a Novel Transcriptional Regulation of NDRG1 Under Normoxia and Hypoxia in MCF-7 Breast Cancer Cells |
title_short |
Identification of the Cellular Function and a Novel Transcriptional Regulation of NDRG1 Under Normoxia and Hypoxia in MCF-7 Breast Cancer Cells |
title_full |
Identification of the Cellular Function and a Novel Transcriptional Regulation of NDRG1 Under Normoxia and Hypoxia in MCF-7 Breast Cancer Cells |
title_fullStr |
Identification of the Cellular Function and a Novel Transcriptional Regulation of NDRG1 Under Normoxia and Hypoxia in MCF-7 Breast Cancer Cells |
title_full_unstemmed |
Identification of the Cellular Function and a Novel Transcriptional Regulation of NDRG1 Under Normoxia and Hypoxia in MCF-7 Breast Cancer Cells |
title_sort |
identification of the cellular function and a novel transcriptional regulation of ndrg1 under normoxia and hypoxia in mcf-7 breast cancer cells |
publishDate |
2014 |
url |
http://ndltd.ncl.edu.tw/handle/83722722442952786789 |
work_keys_str_mv |
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