Research Papers:

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

Erik Hilborn _, Olle Stål, Andrey Alexeyenko and Agneta Jansson

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Oncotarget. 2017; 8:62183-62194. https://doi.org/10.18632/oncotarget.19136

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Erik Hilborn1, Olle Stål1, Andrey Alexeyenko2,3 and Agneta Jansson1

1Department of Clinical and Experimental Medicine and Department of Oncology, Faculty of Health Sciences, Linköping University, Linköping, Sweden

2Department of Microbiology, Tumor and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden

3National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Solna, Sweden

Correspondence to:

Erik Hilborn, email: [email protected]

Keywords: breast cancer, HSD17B1, HSD17B2, miRNA

Received: September 23, 2016    Accepted: June 01, 2017    Published: July 10, 2017


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 HSD17B1 expression and had a time-dependent effect on HSD17B2 expression. This effect was lost in estrogen receptor-α down-regulated or negative cell lines. Dihydrotestosterone treatment increased HSD17B2 expression, with limited effect on HSD17B1 expression. No effect was seen in cells without AR or in combination with the AR inhibitor hydroxyflutamide. The miRNA-17 up-regulated HSD17B1, while miRNA-210 and miRNA-7-5p had up- and down-regulatory effect and miRNA-1304-3p reduced HSD17B1 expression. The miRNA-204-5p, 498, 205-3p and 579-3p reduced HSD17B2 expression. Downregulation of CX3CL1, EPHB6, and TP63 increased HSD17B1 and HSD17B2 expression, while GREB1 downregulation suppressed HSD17B1 and promoted HSD17B2 expression.

Conclusion: We show that HSD17B1 and HSD17B2 are controlled by estradiol, dihydrotestosterone, and miRNAs, as well as modulated by several breast cancer-related genes, which could have future clinical applications.

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