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MTA1 Promotes Autophagy and Resistance to Tamoxifen in ERα-Positive Breast Cancer Cell Line
유방암 세포주에서 MTA1에 의한 자가포식작용과 타목시펜 내성 유발

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Authors
Koh, Dahae
Advisor
이미옥
Major
약학대학 약학과
Issue Date
2015-08
Publisher
서울대학교 대학원
Keywords
MTA1AutophagyTamoxifen resistanceBreast Cancer
Description
학위논문 (석사)-- 서울대학교 대학원 : 약학과(병태생리학전공), 2015. 8. 이미옥.
Abstract
Autophagy, a cellular recycling process in which long-lived proteins and organelles are degraded, has recently been recognized to be associated with drug resistance in various cancers. Several studies have reported an increase in autophagy in tamoxifen-resistant breast cancer. Interestingly, we found metastasis-associated protein 1 (MTA1) to be overexpressed in tamoxifen-resistant MCF7 breast cancer cell line, raising a potential link between MTA1 overexpression and the autophagy-induced tamoxifen resistance. To investigate the involvement of MTA1 in tamoxifen resistance, we used RNA interference against MTA1 followed by 4-hydroxytamoxifen (4OHT) treatment in MCF7 cells. Our data showed that MTA1 knockdown sensitized cells to 4OHT. Moreover, we observed that the depletion of MTA1 resulted in the decrease in autophagic flux. The reduction was accompanied with the downregulation of LC3-II level, a well-known marker for autophagy. 4OHT is known to induce autophagy in cells, which is a stress response in order to maintain cellular homeostasis. However, 4OHT-induced autophagy is known to ironically lead to the resistance to the drug. Our data showed that MTA1 knockdown led to a decrease in 4OHT-induced autophagy. Through qRT-PCR experiment, we observed that MTA1 depletion correlated with the decrease in the upregulation of ATG9B, an autophagy-related gene involved in the recycling of LC3 protein, in the presence of 4OHT. Our observations may help to understand the role of MTA1 in the development of resistance to endocrine therapy for patients with ERα-positive breast cancer.
Language
English
URI
https://hdl.handle.net/10371/133606
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College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Theses (Master's Degree_약학과)
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