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KLF4在来曲唑耐药性乳腺癌病理组织中的表达与作用
引用本文:赵 戈,樊 菁,孟慧敏,崔风强,巫 姜,李松朋,王 敏,王 廷. KLF4在来曲唑耐药性乳腺癌病理组织中的表达与作用[J]. 现代生物医学进展, 2019, 19(4): 614-619
作者姓名:赵 戈  樊 菁  孟慧敏  崔风强  巫 姜  李松朋  王 敏  王 廷
作者单位:中国人民解放军空军军医大学西京医院甲乳外科;中国人民解放军空军军医大学西京医院消化二科;
基金项目:国家自然科学基金项目(30570982)
摘    要:目的:探讨转录因子KLF4在来曲唑(Letrozole)耐药性乳腺癌(breast cancer, BCa)病理组织和细胞中的表达特点及其在来曲唑耐药性病理发生过程中的作用特点及机制。方法:采用实时定量PCR、Western blotting和免疫组织化学法检测KLF4在来曲唑耐药性BCa病理组织和细胞中的表达特点;MTT和细胞凋亡ELISA法检测过表达外源性KLF4对BCa细胞来曲唑药物的影响;荧光素酶报告基因活性检测分析KLF4对编码雌激素受体α(ER-α)的ESR1的转录激活作用。结果:KLF4在来曲唑耐药性乳腺癌病理组织及细胞中呈异常高表达(P0.05);采用10-5 M的来曲唑处理MCF7细胞可显著抑制细胞活力,并促进细胞发生凋亡,而在细胞中过表达外源性KLF4后,这一来曲唑毒性作用可被有效逆转(P0.05),细胞活力甚至恢复到来曲唑未处理前状态;荧光素酶报告基因活性检测显示在外源性雌激素E2刺激下,GLucONTM-ESR1报告载体的荧光素酶活性显著升高,这一升高趋势可被10-5 M的来曲唑处理有效抑制;当转染外源性KLF4后,来曲唑对GLucONTM-ESR1报告载体的荧光素酶活性的抑制效应被进一步加强(P0.01)。结论:KLF4可能通过转录调控作用直接抑制ER-α表达及活性,进而参与对来曲唑耐药性病理发生过程的关键调节作用。

关 键 词:乳腺癌;来曲唑;KLF4;雌激素受体;转录调控
收稿时间:2018-08-04
修稿时间:2018-08-28

Expression and Functional Analysis of KLF4 in Letrozole-Resistant Breast Cancer
ZHAO Ge,FAN Jing,MENG Hui-min,CUI Feng-qiang,WU Jiang,LI Song-peng,WANG Min and WANG Ting. Expression and Functional Analysis of KLF4 in Letrozole-Resistant Breast Cancer[J]. Progress in Modern Biomedicine, 2019, 19(4): 614-619
Authors:ZHAO Ge  FAN Jing  MENG Hui-min  CUI Feng-qiang  WU Jiang  LI Song-peng  WANG Min  WANG Ting
Affiliation:Department of Thyroid Gland and Breast Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi''an, Shaanxi, 710032, China,Department of Thyroid Gland and Breast Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi''an, Shaanxi, 710032, China,Department of Thyroid Gland and Breast Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi''an, Shaanxi, 710032, China,Department of Thyroid Gland and Breast Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi''an, Shaanxi, 710032, China,Department of Thyroid Gland and Breast Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi''an, Shaanxi, 710032, China,Department of Thyroid Gland and Breast Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi''an, Shaanxi, 710032, China,Department of Gastroenterology Division 2, Xijing Hospital, Fourth Military Medical University, Xi''an, Shaanxi, 710032, China and Department of Thyroid Gland and Breast Vascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi''an, Shaanxi, 710032, China
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