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[1]柴慈曼,尚志群,牛远杰.FKBP51表达降低促进雌激素受体阳性乳腺癌他莫昔芬耐药机制初探[J].天津医科大学学报,2019,25(06):559-562+576.
 CHAI Ci-man,SHANG Zhi-qun,NIU Yuan-jie.Effect of FKBP51 on tamoxifen resistance in estrogen receptor positive breast cancer[J].Journal of Tianjin Medical University,2019,25(06):559-562+576.
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FKBP51表达降低促进雌激素受体阳性乳腺癌他莫昔芬耐药机制初探(PDF)
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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
25
期数:
2019年06期
页码:
559-562+576
栏目:
基础医学
出版日期:
2019-11-20

文章信息/Info

Title:
Effect of FKBP51 on tamoxifen resistance in estrogen receptor positive breast cancer
文章编号:
1006-8147(2019)06-0559-05
作者:
柴慈曼12尚志群2牛远杰2
(1.天津医科大学第二医院甲状腺乳腺外科,天津300211;2.天津市泌尿外科研究所,天津300211)
Author(s):
CHAI Ci-man12 SHANG Zhi-qun2 NIU Yuan-jie2
(1.Department of Breast and Thyroid Surgery, The Second Hospital of Tianjin Medical University, Tianjin 300211, China; 2. Tianjin Institute of Urology, Tianjin 300211, China)
关键词:
FK506结合蛋白51雌激素受体乳腺癌他莫昔芬AKT信号通路
Keywords:
FK506 binding protein 51estrogen receptorbreast cancertamoxifenAKT signaling pathway
分类号:
R737.9
DOI:
-
文献标志码:
A
摘要:
目的:初步探讨FK506结合蛋白51(FKBP51)在雌激素受体阳性(ER+)乳腺癌他莫昔芬耐药中的作用及分子机制。方法:采用ER+人乳腺癌MCF-7细胞建立对他莫昔芬耐药的MCF-7/TAMR细胞,MTT法检测他莫昔芬对MCF-7和MCF-7/TAMR细胞增殖的影响。Western blot检测FKBP51和蛋白激酶B(AKT)信号通路中相关蛋白在MCF-7和MCF-7/TAMR细胞中的表达情况。通过敲低或者过表达FKBP51,观察FKBP51对ER+乳腺癌细胞耐药性及AKT信号通路的影响。在ER+人乳腺癌组织标本中验证FKBP51表达情况。结果:成功建立MCF-7/TAMR细胞株。他莫昔芬对MCF-7和MCF-7/TAMR细胞增殖的抑制率均呈剂量依赖性,且对MCF-7细胞增殖的抑制率高于MCF-7/TAMR细胞(P<0.05)。Western blot结果显示,FKBP51在MCF-7/TAMR细胞中的表达低于MCF-7细胞,并且其表达水平的降低激活AKT信号通路的活性,促进乳腺癌细胞对他莫昔芬的耐药。同时,FKBP51在ER+他莫昔芬耐药人乳腺癌组织中表达水平低于他莫昔芬敏感人乳腺癌组织。结论:FKBP51表达水平降低促进ER+乳腺癌患者对他莫昔芬耐药,可能与激活细胞内AKT信号通路有关。
Abstract:
Objective: To explore the effect of FK506 binding protein 51 (FKBP51) on tamoxifen resistance in estrogen receptor positive (ER+) breast cancer and its mechanism. Methods: The ER+ human breast cancer MCF-7 cells was used to establish tamoxifen-resistant MCF-7/TAMR cell line. The effect of tamoxifen on the proliferation of MCF-7 and MCF-7/TAMR cells was detected by MTT method. Western blot was used to detect the expressions of FKBP51 and the associated proteins in AKT signaling in MCF-7 and MCF-7/TAMR cells.Results: The MCF-7/TAMR cell line was successfully established. The inhibitory rates of tamoxifen on the proliferation of two breast cancer cells were in a dose-dependent manner, which on MCF-7 cells was significantly higher than that on MCF-7/TAMR cells(P<0.05). Western blot results showed that the expression of FKBP51 in MCF-7/TAMR cells was significantly lower than that in MCF-7 cells. Compared with MCF-7 cells, AKT signaling increased in MCF-7/TAMR cells. Conclusion: lower FKBP51 expression promotes tamoxifen resistance in patients with ER+ breast cancer, which may be related to activation of AKT signaling pathway.

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备注/Memo

备注/Memo:
基金项目 天津医科大学第二医院青年基金项目(2017ydey05)
作者简介 柴慈曼(1985-),女,医师,博士在读,研究方向:肿瘤内分泌耐药机制;通信作者:牛远杰,E-mail:m15122901226@163.com。
更新日期/Last Update: 2020-01-20