MTDH Mediates Estrogen-Independent Growth and Tamoxifen Resistance by Down-Regulating PTEN in MCF-7 Breast Cancer Cells
Background: About 70% of human breast cancers express estrogen receptor α (ERα) and in this kind of breast cancer estrogen plays an important role. Estrogen independent growth has been reported to promote resistance to one of the selective estrogen receptor modulators (SERMs) tamoxifen which is clin...
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Cell Physiol Biochem Press GmbH & Co KG
2014-05-01
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doaj-e2f6a5ac103a404dbd247429da2ebf2e2020-11-25T01:09:43ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782014-05-013351557156710.1159/000358719358719MTDH Mediates Estrogen-Independent Growth and Tamoxifen Resistance by Down-Regulating PTEN in MCF-7 Breast Cancer CellsChunyuan XuXiaoli KongHaiji WangNing ZhangXiangnan KongXia DingXiaoyan LiQifeng YangBackground: About 70% of human breast cancers express estrogen receptor α (ERα) and in this kind of breast cancer estrogen plays an important role. Estrogen independent growth has been reported to promote resistance to one of the selective estrogen receptor modulators (SERMs) tamoxifen which is clinically the first line treatment for patients with ERα-positive breast cancer. The resistance of tamoxifen is a major problem in the clinical management of breast cancer. Methods: We used MCF-7 cells with ectopic expression of MDTH in this study. MTT, clone formation and tumor formation in nude mice methods were utilized to confirm the role of MTDH in estrogen-independent growth and tamoxifen resistance. Flow cytometry, western blot and siRNA were used to study the detailed mechanisms. Results: We found that MTDH could mediate estrogen-independent growth and induce resistance to tamoxifen in ERα-positive breast cancer cells. MTDH could reduce the expression of PTEN, up-regulate AKT and BCL2 and inhibit the apoptosis induced by tamoxifen. Conclusion: Our study indicated that MTDH was a candidate marker to predict the clinical efficacy of tamoxifen and targeting MTDH would overcome the resistance to tamoxifen in breast cancer cells.http://www.karger.com/Article/FullText/358719MTDHEstrogen-independent growthTamoxifen resistancePTENBreast cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chunyuan Xu Xiaoli Kong Haiji Wang Ning Zhang Xiangnan Kong Xia Ding Xiaoyan Li Qifeng Yang |
spellingShingle |
Chunyuan Xu Xiaoli Kong Haiji Wang Ning Zhang Xiangnan Kong Xia Ding Xiaoyan Li Qifeng Yang MTDH Mediates Estrogen-Independent Growth and Tamoxifen Resistance by Down-Regulating PTEN in MCF-7 Breast Cancer Cells Cellular Physiology and Biochemistry MTDH Estrogen-independent growth Tamoxifen resistance PTEN Breast cancer |
author_facet |
Chunyuan Xu Xiaoli Kong Haiji Wang Ning Zhang Xiangnan Kong Xia Ding Xiaoyan Li Qifeng Yang |
author_sort |
Chunyuan Xu |
title |
MTDH Mediates Estrogen-Independent Growth and Tamoxifen Resistance by Down-Regulating PTEN in MCF-7 Breast Cancer Cells |
title_short |
MTDH Mediates Estrogen-Independent Growth and Tamoxifen Resistance by Down-Regulating PTEN in MCF-7 Breast Cancer Cells |
title_full |
MTDH Mediates Estrogen-Independent Growth and Tamoxifen Resistance by Down-Regulating PTEN in MCF-7 Breast Cancer Cells |
title_fullStr |
MTDH Mediates Estrogen-Independent Growth and Tamoxifen Resistance by Down-Regulating PTEN in MCF-7 Breast Cancer Cells |
title_full_unstemmed |
MTDH Mediates Estrogen-Independent Growth and Tamoxifen Resistance by Down-Regulating PTEN in MCF-7 Breast Cancer Cells |
title_sort |
mtdh mediates estrogen-independent growth and tamoxifen resistance by down-regulating pten in mcf-7 breast cancer cells |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2014-05-01 |
description |
Background: About 70% of human breast cancers express estrogen receptor α (ERα) and in this kind of breast cancer estrogen plays an important role. Estrogen independent growth has been reported to promote resistance to one of the selective estrogen receptor modulators (SERMs) tamoxifen which is clinically the first line treatment for patients with ERα-positive breast cancer. The resistance of tamoxifen is a major problem in the clinical management of breast cancer. Methods: We used MCF-7 cells with ectopic expression of MDTH in this study. MTT, clone formation and tumor formation in nude mice methods were utilized to confirm the role of MTDH in estrogen-independent growth and tamoxifen resistance. Flow cytometry, western blot and siRNA were used to study the detailed mechanisms. Results: We found that MTDH could mediate estrogen-independent growth and induce resistance to tamoxifen in ERα-positive breast cancer cells. MTDH could reduce the expression of PTEN, up-regulate AKT and BCL2 and inhibit the apoptosis induced by tamoxifen. Conclusion: Our study indicated that MTDH was a candidate marker to predict the clinical efficacy of tamoxifen and targeting MTDH would overcome the resistance to tamoxifen in breast cancer cells. |
topic |
MTDH Estrogen-independent growth Tamoxifen resistance PTEN Breast cancer |
url |
http://www.karger.com/Article/FullText/358719 |
work_keys_str_mv |
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