PES1 Promotes the Proliferation, Invasion and Migration of Papillary Thyroid Cancer by Upregulating the ERα/ERβ Protein Ratio
- VernacularTitle:PES1 上调ERα/ERβ 蛋白比率促进甲状腺乳头状癌细胞增殖和侵袭迁移
- Author:
Long CHENG
1
;
Yi-bo QIU
2
;
Lin-wan XU
2
;
Zhi-min LIU
2
Author Information
1. 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
2. Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China
- Publication Type:Journal Article
- Keywords:
PES1;
ERα;
ERβ;
papillary thyroid carcinoma
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2020;41(4):515-524
- CountryChina
- Language:Chinese
-
Abstract:
【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 BRAFV600E 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/ERβ protein 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 PES1 significantly enhanced the proliferation, invasion and migration of papillary thyroid carcinoma cells. 【Conclusions】 ERα and ERβ are co-expressed in human PTC tissues and cells. PES1 modulates the balance between ERα and ERβ by elevating the ERα protein level and simultaneously reducing the ERβ protein level, then up-regulating the ERα/ERβ protein ratio and promoting the proliferation, invasion and migration of PTC cells, and then promoting the occurrence and development of PTC.
