Selective estrogen receptor modulators decrease invasiveness in pituitary adenoma cell lines AtT‐20 and TtT/GF by affecting expression of MMP‐14 and ADAM12,FEBS Open Bio

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Selective estrogen receptor modulators decrease invasiveness in pituitary adenoma cell lines AtT‐20 and TtT/GF by affecting expression of MMP‐14 and ADAM12
FEBS Open Bio ( IF 2.8 ) Pub Date : 2020-10-08 , DOI: 10.1002/2211-5463.12999
Zhuo Zhang _{1,

2} , Jörg W Bartsch ₁ , Julia Benzel _{1,

3} , Ting Lei ₂ , Christopher Nimsky ₁ , Benjamin Voellger ₁

Affiliation

Selective estrogen receptor modulators (SERMs) significantly affect survival and invasiveness of rodent pituitary adenoma (PA) cells. The impact of three clinically relevant SERMs (bazedoxifene, clomiphene, raloxifene) on invasiveness and on gene and protein expression of invasion‐related proteases [matrix metalloproteinase‐14 (MMP‐14) and A disintegrin and metalloproteinase‐12 (ADAM12)] was analyzed in murine PA cells (AtT‐20 and TtT/GF). All SERMs significantly decreased cell invasiveness. Moreover, SERMs significantly decreased expression of ADAM12 mRNA in both cell lines and of MMP‐14 mRNA in TtT/GF cells. Invasion rates of AtT‐20 and TtT/GF significantly decreased after ADAM12 gene silencing, and the invasion rate of TtT/GF cells significantly decreased after MMP‐14 gene silencing. All SERMs affected ADAM12 protein expression in AtT‐20 cells whereas bazedoxifene and raloxifene decreased MMP‐14 protein expression in TtT/GF cells. We conclude that SERMs attenuate invasiveness of murine PA cells by downregulating expression levels of invasion‐related proteases MMP‐14 and ADAM12.

中文翻译：

选择性雌激素受体调节剂通过影响 MMP-14 和 ADAM12 的表达来降低垂体腺瘤细胞系 AtT-20 和 TtT/GF 的侵袭性

选择性雌激素受体调节剂 (SERM) 显着影响啮齿动物垂体腺瘤 (PA) 细胞的存活和侵袭性。分析了三种临床相关的 SERM（巴多昔芬、克罗米芬、雷洛昔芬）对侵袭性以及侵袭相关蛋白酶 [基质金属蛋白酶-14 (MMP-14) 和 A 去整合素和金属蛋白酶-12 (ADAM12)] 基因和蛋白质表达的影响在鼠 PA 细胞（AtT-20 和 TtT/GF）中。所有 SERM 均显着降低细胞侵袭性。此外，SERM 显着降低了两种细胞系中 ADAM12 mRNA 和 TtT/GF 细胞中 MMP-14 mRNA 的表达。ADAM12基因沉默后AtT-20和TtT/GF的侵袭率显着降低，MMP-14基因沉默后TtT/GF细胞的侵袭率显着降低。所有 SERM 均影响 AtT-20 细胞中的 ADAM12 蛋白表达，而巴多昔芬和雷洛昔芬降低 TtT/GF 细胞中 MMP-14 蛋白的表达。我们得出结论，SERM 通过下调侵袭相关蛋白酶 MMP-14 和 ADAM12 的表达水平来减弱小鼠 PA 细胞的侵袭性。

更新日期：2020-11-04

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