Mechanism Of 17β-estradiol Promoted Proliferation And Invasion Of Papillary Thyroid Carcinoma Through Estrogen Receptor Alpha-36

Objection: To investigate the effect of estrogen receptor-α36(ERα36)on 17β-estradiol(E2)promoted proliferation and invasion of papillary thyroid carcinoma(PTC).Methods: Immunohistochemistry was used to analyze the expression of ERα36,EGFR and HER2 in 218 PTC samples.The correlations of ERα36,EGFR and HER2 expression with one another,and with several clinicopathological indicators were statistically analyzed.Expression of ERα36 in BCPAP and K-1 cell lines were detected by Western blot.The levels of phosphorylated ERK1/2,phosphorylated AKT,nuclear translocation of NF-κB and levels of Cyclin Dl,Survivin,MMP2 were analyzed by Western blot.BCPAP and K-1 cells were divided into groups,respectively: control,E2,E2+scrambled siRNA,E2+ERα36-siRNA.The effect of ERα36-siRNA was tested by Western blot.Proliferation of BCPAP cells was measured by MTT method.The invasion and migration ability were determined by Transwell/Matrigel assay.Results: Positive expression rates of ERα36,EGFR and HER2 in 218 cases of PTC were 112(51.4%),132(60.6%)and 135(61.9%),significantly lower than those of the normal and nodular hyperplasia tissues.ERα36,EGFR and HER2 expression had significant correlations with TNM stages(P < 0.001)and cervical lymph node metastasis(P < 0.001).Meanwhile,ERα36 expression had a positive correlation with EGFR(rs =0.252,P < 0.001)and EGFR(rs = 0.352,P < 0.001).Concomitant expression of any two or all of the three molecules had stronger correlation with lymph node metastasis and TNM stage than did each alone(P < 0.001).BCPAP and K-1 cells expressed ERα36.E2 promoted the expression of ERα36 in BCPAP and K-1 cells,and 10-8mol/L E2 for 24 h exhibited the most effective results.After exposure to E2 at different time point,the rapid phosphorylation of ERK and AKT were observed at 15 and 10 min.E2 induced nuclear translocation of NF-κB and increased expression levels of Cyclin Dl,Survivin,MMP2.ERα36-si RNA inhibited these promotion.E2-induced cell proliferation and invasion/migration were suppressed by ERα36-siRNA.Conclusion: The high expression of ERα36,EGFR and HER2 was correlated with lymph node metastasis in PTC patients.Meanwhile,E2 may promoted proliferation and invasion/migration through ERα36.