中国癌症杂志 ›› 2021, Vol. 31 ›› Issue (3): 161-169.doi: 10.19401/j.cnki.1007-3639.2021.03.001

• 论著 • 上一篇    下一篇

TRIP6在乳腺癌中的作用及其机制研究

王春建 1 ,聂 刚 2 ,毛 艳 2   

  1. 1. 山东省肿瘤医院乳腺科,山东 济南 250000 ;
    2. 青岛大学附属医院乳腺病诊疗中心,山东 青岛 266555
  • 出版日期:2021-03-30 发布日期:2021-04-01
  • 通信作者: 聂 刚 E-mail: yuzhimu37552434@163.com
  • 基金资助:
    山东省自然科学基金(ZR2017BH061)。

The role of TRIP6 in breast cancer and its mechanism

WANG Chunjian 1 , NIE Gang 2 , MAO Yan   

  1. 1. Department of Breast, Shandong Cancer Hospital, Jinan 250000, Shandong Province, China; 2. Breast Center, Qingdao University Affiliated Hospital, Qingdao 266555, Shandong Province, China
  • Online:2021-03-30 Published:2021-04-01
  • Contact: NIE Gang E-mail: yuzhimu37552434@163.com

摘要: 背景与目的:甲状腺激素及其受体与乳腺癌关系密切,甲状腺激素受体相互作用蛋白6(thyroid receptor-interacting protein 6,TRIP6)可能通过与甲状腺受体相互作用促进乳腺癌的发生、发展。探讨TRIP6在乳腺癌中的作用及可能机制。方法:采用免疫组织化学染色法检测2011年1月—2013年12月山东省肿瘤医院手术切除的268例乳腺癌组织及其配对的癌旁组织、80例乳腺良性纤维腺瘤组织中TRIP6和转录因子叉头框蛋白C1(forkhead box C1,FOXC1)的表达。用COX比例风险回归模型和Kaplan-Meier法分析乳腺癌患者的生存预后。采用蛋白质印迹法(Western blot)检测正常乳腺上皮细胞MCF-10A和乳腺癌细胞(BT474、MCF7和MDA-MB-231)中TRIP6和FOXC1的表达。用TRIP6 si-RNA和si-control分别转染MDA-MB-231细胞,采用克隆形成实验和细胞计数试剂盒-8(cell counting kit-8,CCK-8)实验检测细胞增殖,采用transwell小室实验检测细胞侵袭,采用细胞划痕实验检测细胞迁移,采用Western blot检测FOXC1蛋白的相对表达量。结果:乳腺癌组织中TRIP6和FOXC1的阳性表达率分别为85.08%和88.06%,均高于乳腺良性纤维腺瘤组织(25.00%和15.00%)和乳腺癌癌旁组织(55.97%和62.31%)(P均<0.01)。乳腺癌组织TRIP6与FOXC1的阳性表达率呈正相关(r=0.771,P<0.001)。TRIP6高表达和FOXC1高表达是乳腺癌患者总生存期和无进展生存期的独立影响因素(P均<0.05)。TRIP6高表达乳腺癌患者的总生存率和无进展生存率均低于TRIP6低表达患者(P均<0.001);FOXC1高表达乳腺癌患者的总生存率和无进展生存率均低于FOXC1低表达患者(P均<0.001)。BT474、MCF7和MDA-MB-231细胞的TRIP6和FOXC1蛋白相对表达量均高于MCF-10A细胞(P均<0.05)。MDA-MB-231细胞中TRIP6和FOXC1蛋白相对表达量呈正相关(r=0.908,P=0.033)。TRIP6 si-RNA组克隆细胞数、增殖活力、细胞侵袭数、细胞迁移率和FOXC1蛋白相对表达量均低于si-control组(P均<0.05)。结论:TRIP6可能通过FOXC1参与乳腺癌的发生、发展过程,其高表达预示着患者预后不良。

关键词: 甲状腺激素受体相互作用蛋白6, 叉头框蛋白C1, 乳腺癌, 增殖, 侵袭, 迁移, 预后

Abstract: Background and purpose: Thyroid hormone and its receptors are closely related to breast cancer. Thyroid receptor-interacting protein 6 (TRIP6) may promote the occurrence and development of breast cancer by interacting with thyroid receptor. This study aimed to investigate the role of TRIP6 in breast cancer and its possible mechanism. Methods: Immunohistochemical staining was used to detect the expressions of TRIP6 and the transcription factor forkhead box C1 (FOXC1) in 268 breast cancer tissues, their matched adjacent tissues and 80 benign fibroadenoma tissues that were resected in Shandong Cancer Hospital from January 2011 to December 2013. COX proportional hazards regression model and Kaplan-Meier method were used to analyze the survival prognosis of breast cancer patients. The expressions of TRIP6 and FOXC1 in normal breast epithelial cells MCF-10A and breast cancer cells (BT474, MCF7 and MDA-MB-231) were detected by Western blot. MDA-MB-231 cells were transfected with TRIP6 si-RNA and si-control respectively, and cell proliferation was detected by clone formation experiment and cell counting kit-8 (CCK-8) experiment. Cell invasion was detected by transwell cell experiment. Cell migration was detected by cell scratch experiment. Western blot was used to detect relative expression of FOXC1 protein. Results: The positive expression rates of TRIP6 and FOXC1 in breast cancer tissues were 85.08% and 88.06%, respectively, which were higher than those in benign fibroadenoma (25.00% and 15.00%) and paracancerous tissues (55.97% and 62.31%) (all P<0.01). The positive expression rates of TRIP6 and FOXC1 in breast cancer tissues were positively correlated (r=0.771, P<0.001). High expressions of TRIP6 and FOXC1 were independent factors affecting the overall survival and progression-free survival of breast cancer patients (both P<0.05). The overall survival rate and progression-free survival rate of breast cancer patients with high expression of TRIP6 were lower than those of patients with low expression of TRIP6 (all P<0.001). The overall survival rate and progression-free survival rate of breast cancer patients with high expression of FOXC1 were lower compared with patients with low expression of FOXC1 (all P<0.001). The relative protein expression levels of TRIP6 and FOXC1 were higher in BT474, MCF7 and MDA-MB-231 cells than in MCF10A cells (all P<0.05). The relative protein expressions of TRIP6 and FOXC1 in MDA-MB-231 cells were positively correlated (r=0.908, P=0.033). The number of cloned cells, proliferation viability, cell invasion, cell migration rate and relative protein expression of FOXC1 were all lower in the TRIP6 si-RNA group than in the si-control group (all P<0.05). Conclusion: TRIP6 may participate in the occurrence and development of breast cancer through FOXC1, and its high expression indicates that the survival prognosis of patient is poor.

Key words: Thyroid receptor-interacting protein 6, Forkhead box C1, Breast cancer, Proliferation, Invasion, Migration, Prognosis