雌二醇、双氢睾酮、微小RNA以及与乳腺癌相关基因对乳腺癌细胞系中1型和2型羟基类固醇17β-脱氢酶基因表达的调控

The regulation of hydroxysteroid 17β-dehydrogenase type 1 and 2 gene expression in breast cancer cell lines by estradiol, dihydrotestosterone, microRNAs, and genes related to breast cancer.

作者信息

Hilborn Erik, Stål Olle, Alexeyenko Andrey, Jansson Agneta

机构信息

Department of Clinical and Experimental Medicine and Department of Oncology, Faculty of Health Sciences, Linköping University, Linköping, Sweden.

Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden.

出版信息

Oncotarget. 2017 Jul 10;8(37):62183-62194. doi: 10.18632/oncotarget.19136. eCollection 2017 Sep 22.

AIM

To investigate the influence of estrogen, androgen, microRNAs, and genes implicated in breast cancer on the expression of HSD17B1 and HSD17B2.

MATERIALS

Breast cancer cell lines ZR-75-1, MCF7, T47D, SK-BR-3, and the immortalized epithelial cell line MCF10A were used. Cells were treated either with estradiol or dihydrotestosterone for 6, 24, 48 hours, or 7 days or treated with miRNAs or siRNAs predicted to influence HSD17B expression Results and discussion. Estradiol treatment decreased expression and had a time-dependent effect on . This effect was lost in estrogen receptor-α down-regulated or negative cell lines. Dihydrotestosterone treatment increased expression, with limited effect on expression. No effect was seen in cells without AR or in combination with the AR inhibitor hydroxyflutamide. The up-regulated , while and had up- and down-regulatory effect and reduced expression. The and reduced expression. Downregulation of CX3CL1, EPHB6, and TP63 increased and , while downregulation suppressed and promoted expression.

CONCLUSION

We show that and are controlled by estradiol, dihydrotestosterone, and miRNAs, as well as modulated by several breast cancer-related genes, which could have future clinical applications.

目的

研究雌激素、雄激素、微小RNA以及与乳腺癌相关的基因对17β-羟类固醇脱氢酶1（HSD17B1）和17β-羟类固醇脱氢酶2（HSD17B2）表达的影响。

材料

使用乳腺癌细胞系ZR-75-1、MCF7、T47D、SK-BR-3以及永生化上皮细胞系MCF10A。细胞分别用雌二醇或双氢睾酮处理6、24、48小时或7天，或用预测会影响HSD17B表达的微小RNA（miRNA）或小干扰RNA（siRNA）处理。结果与讨论。雌二醇处理降低了表达，并对……有时间依赖性影响。这种作用在雌激素受体-α下调或阴性的细胞系中消失。双氢睾酮处理增加了……的表达，对……表达的影响有限。在没有雄激素受体（AR）的细胞或与AR抑制剂羟基氟他胺联合处理的细胞中未观察到作用。……上调了……，而……和……具有上调和下调作用，……降低了……的表达。……和……降低了……的表达。CX3CL1、EPHB6和TP63的下调增加了……和……，而……的下调抑制了……并促进了……的表达。