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성장인자 수용체 HER2 발현에 따른 에스트로젠 수용체의 전사 활성도 변화와 임상적 의의

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 The effect of growth factor receptor HER2 on the estrogen receptor transcriptional activities and its implications 
 허민규  ;  박순옥  ;  정소영  ;  김승일  ;  박병우 
 JOURNAL OF BREAST CANCER, Vol.8(3) : 105-112, 2005 
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Purpose : Until recently, breast cancer carcinogenesis has not been fully understood, but the roles of estrogen receptors(ERs) and growth factor receptors(like HER2) were known to be important. Growth factors have been shown to synergize in the E2 signaling pathway, although the actual molecular mechanism remains largely unknown. To investigate the effect of HER2 overexpression on the ERE(estrogen responsive element)-mediated transcriptional activity of the ERs, this study was designed. Methods : NIH3T3 cells, T6-17 cells (NIH3T3 cells with stably transfected with HER2), and MCF-7 cells were maintained in dextran-coated charcoal stripped 10% Dulbecco’s Modified Eagle Medium (DMEM). Transient transfection of constructs (pcDNA3-ER, pcDNA3-ER, pERE-luc, pAP-1-luciferase, and pcDNA-HER2) into each cells was performed using the Lipofectamine PLUSTM system. Reporter gene assays using ERE-luciferase or AP-1-luciferase were used to measure the ER transcriptional activities after treatment with estradiol (E2) and tamoxifen. Results : Reporter gene assay using ERE-luciferase in both ER and ER, showed much less responsiveness to estrogen in HER2 overexpressing T6-17 cells than in NIH3T3 cells, but there was no remarkable difference after treatment with tamoxifen. The AP-1-mediated transcriptional activity was increased in ER after tamoxifen treatment, but it disappeared in HER2-expressing T6-17 cells. The responsiveness to estrogen in HER2-transfected MCF-7 cells was also slightly less than in the control MCF-7 cells, and the ERE-mediated transcriptional activity of estrogen in MCF-7 cells was decreased, in a dose-dependent manner, after HER2 transfection. Conclusion : Coexpression of HER2 and ER seems to make cells less responsive to estrogen stimulation, and decrease the ERE-mediated transcriptional activity in both ER and ER. These results suggest that the expression of HER2 reduces the estrogen dependency in cell growth and eventually induces estrogen independent-growth.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Seung Il(김승일)
Park, Byeong Woo(박병우) ORCID logo https://orcid.org/0000-0003-1353-2607
Jung, So Young(정소영)
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