甲状腺激素对乳腺癌细胞中雌激素受体α和甲状腺激素受体β的影响

Effects of triiodothyronine on estrogen receptor-α and thyroid hormone receptor-β in breast cancer cells

背景与目的:目前,甲状腺激素对乳腺肿瘤的影响尚不明确。本实验目的是研究乳腺癌细胞系中雌激素受体α(ER-α)和甲状腺激素受体β(TR-β)的表达水平及相互关系,观察经甲状腺激素(T3)刺激后,激素受体表达水平的改变,探索受体表达水平改变的可能机制。方法:通过实时定量PCR(realtimePCR)测定7株乳腺癌细胞系中ER-α和TR-β的mRNA水平,观察T3刺激对ER-α、TR-β和视黄醛衍生物X受体α(RXR-α)的表达水平的调节,并测定T3作用后在SK-BR-3细胞中多个基因表达谱。结果:在SK-BR-3、MDA-MB-231和MDA-MB-435中ER-α和TR-β低水平表达,MCF7、BT20、BT474和T47D中ER-α和TR-β均高水平表达。受T3刺激后,ER-α(-)的细胞系中ER-α、TR-β和RXR-α表达都受到不同程度的上调,而在ER-α(+)的细胞系中未观察到该现象。SK-BR-3在T3刺激后,E2F1、转化生长因子(TGF)-β1R、TGF-β2R和人端粒酶逆转录酶(hTERT)表达上调,TGF-β1和p21下调。结论:ER-α和TR-β的表达水平在乳腺癌细胞中密切相关,T3对乳腺癌细胞的影响与细胞内源性ER-α水平相关。

Background and purpose： The effects of triiodothyronine（T3） on breasl cancer remain unclear. The aim of this study was to investigate the expression and eorrelation of estrogen receptor-or（ER-a） aud thvrnid hormone receptor-β （TR-β） in breast caneer cell lines, and to determine the changes of relevant receptors expression and its possible mechanism due to T3 treatment. Methods： Real-Time PCR was used to analyze the expressions of ER-α and TR-β at mRNA level in seven breast canc, er cell lines. The expression level of retinoid X receptor-α（RXR-α） and these two receptors ＇after T3 treatment were determined as well. The gene profile was further deterinined in SK-BR-3 cells treated with T3. Results： The expressions of ER-α and TR-β were quite low in SK-BR-3, MDA-MB-231 and MDA-MB-435 cells, but high in MCF7, BT20, BT474 and T47D cells. ER-a, TR-β and RXR-α were upregulated due to T3 treatment in ER-α（-） cells, but not in ER-α（＋） ceils. In SK-BR-3 ceils, T3 treatment led to up-regulation of E2F1, TGF-β R, TGF-β1R and hTERT, but dnwn-regulation of TGF-β and p21. Conclusions： The expressions of ER-α and TR-β are correlated in breast cancer cells： the effect of T3 treatment on hormone receptors is associated with endogenous ER-α level.