摘要
【目的】研究PES1通过上调ERα/ERβ蛋白比率促进甲状腺乳头状癌(PTC)细胞增殖和侵袭转移的分子机制。【方法】用免疫组化法检测PES1、ERα和ERβ在正常甲状腺组织以及PTC组织中的表达情况;用Western blot法分别检测正常甲状腺细胞株Nthy-ori3-1和PTC细胞株BCPAP和K1中PES1、ERα和ERβ的表达情况,以及PES1过表达、PES1下调时对Nthy-ori3-1细胞和BCPAP细胞中ERα、ERβ蛋白表达比率的影响;用MTT以及Transwell小室法检测PES1、ERα和ERβ对PTC细胞增殖、侵袭和迁移的影响。【结果】在PTC组织中PES1和ERα蛋白表达水平显著高于对应的癌旁正常组织,而ERβ蛋白的表达水平明显低于对应的癌旁正常组织;随着PTC患者恶性程度的逐渐增加,PES1和ERα蛋白水平逐渐升高,ERβ蛋白水平逐渐降低,肿瘤大、有ETE、有LNM、高BRAFV600E表达和高TNM分期(Ⅲ-Ⅳ)的PTC患者有较高的PES1和ERα蛋白表达,而ERβ蛋白表达较低;在Nthy-ori3-1细胞中ERα/ERβ蛋白比率显著小于1(≈0.43),而在BCPAP和K1细胞中ERα/ERβ蛋白比率显著大于1(≈2.25,≈2.82),PES1蛋白表达水平与ERα/ERβ蛋白比率呈正相关;PES1过表达使Nthy-ori3-1细胞中ERα/ERβ蛋白比率明显增大(≈2.54);PES1下调使BCPAP细胞中ERα/ERβ蛋白比率明显降低(≈0.41);PES1下调使PTC细胞增殖、侵袭和迁移能力明显减弱,PES1过表达使PTC细胞增殖、侵袭和迁移能力显著增强。【结论】ERα和ERβ在人PTC组织和细胞中共表达,PES1可调节ERα和ERβ之间的平衡,PES1通过升高ERα蛋白水平,同时降低ERβ蛋白水平,进而上调ERα/ERβ蛋白比率,促进PTC细胞的增殖和侵袭迁移。
【Objective】To investigate the molecular mechanism of PES1 promoting the proliferation,invasion and migration of papillary thyroid cancer by upregulating the ERα/ERβ protein ratio.【Methods】The protein expression level of PES1,ERα,and ERβ in normal thyroid tissue specimens and PTC tissue specimens were analyzed by immunohistochemistry. We preformed Western blotting to detect the expression of PES1,ERα and ERβ using human PTC-derived BCPAP and K1 cells and normal thyroid-derived Nthy-ori3-1 cells. In Nthy-ori3-1 and BCPAP cells,Western blot was used to detect the effect of PES1 overexpression and PES1 knockdown on the ratio of ERα and ERβ protein expression. MTT and Transwell were used to measure the effect of PES1,ERα and ERβ on the proliferation,invasion and migration of PTC cells.【Results】The protein expression level of PES1 and ERα in PTC tissues was significantly higher than that in normal adjacent tissues,while the protein expression level of ERβ was significantly lower than that in normal adjacent tissues.PES1 and ERα protein levels were gradually increased and ERβ protein level was decreased with the degree of malignant behavior of PTC patients. And PTC patients with large tumor size,ETE,LNM,high BRAFV600 E expression and high TNM stage(Ⅲ-Ⅳ)had higher rates of high PES1 and ERα protein expression and low ERβ protein expression. In Nthyori3-1 cells ERα/ERβ protein ratio was significantly less than 1(about 0.43),however,in BCPAP and K1 cells ERα/ERβ protein ratio was significantly greater than 1(about 2.25,about 2.82). The protein expression level of PES1 was positively correlated with the protein ratio of ERα/ERβ. The overexpression of PES1 made a significant increase of ERα/ERβprotein ratio in Nthy-ori3-1 cells(about 2.54). The down-regulation of PES1 significantly reduced ERα/ERβ protein ratio in BCPAP cells(about 0.41). The down-regulation of PES1 decreased the proliferation,invasion and migration of papillary thyroid carcinoma cells,while the overexpression of PES
作者
程龙
邱伊波
许琳婉
刘智敏
CHENG Long;QIU Yi-bo;XU Lin-wan;LIU Zhi-min(Molecular Medicine and Cancer Research Center,Chongqing Medical University,Chongqing 400016,China;Department of Surgery for Breast and Thyroid Gland,Second Affiliated Hospital,Chongqing Medical University,Chongqing 400010,China)
出处
《中山大学学报（医学科学版）》
CAS
CSCD
北大核心
2020年第4期515-524,共10页
Journal of Sun Yat-Sen University:Medical Sciences
基金
国家自然科学基金(81272937)。
