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

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

SUBMITTER: Hilborn E

PROVIDER: S-EPMC5617496 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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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.

Hilborn Erik E Stål Olle O Alexeyenko Andrey A Jansson Agneta A

Oncotarget 20170710 37

<h4>Aim</h4>To investigate the influence of estrogen, androgen, microRNAs, and genes implicated in breast cancer on the expression of HSD17B1 and HSD17B2.<h4>Materials</h4>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 ...[more]

PMID: 28977936

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Project description:17Î²-HSD1 expression modulates T47D transcript profile in in steroid-deprived medium. The enzyme specifically regulates apoptosis and cancer-related genes in T47D cells cultured in steroid-deprived medium. Genes that primarily involved in Cell cycle progression, such as the Cyclin A2 gene, CCNA2, are generally down-regulated whereas most genes involved in apoptosis and cell death, such as the proapoptotic gene XAF1 and FGF12, are on the contrary up-regulated by 17Î²-HSD1 knockdown, and 21% of the modulated genes belong to this latter functional category. This correborates with its role previously shown in increasing breast cancer cell proliferation (Aka et al, 2010) and indicates that in addition to its direct role as cell proliferation via incresing E2 and decreasing DHT, 17Î²-HSD1 may also be involved in oncogenesis by favoring its anti-apoptosis pathway in breast cancer cells 17Î²-HSD1 may also be involved in oncogenesis by favoring anti-apoptosis pathway and/or inhibiting cell survival pathway. We tested the ability of estrogen to induce or repress endogenous genes of T47D by microarray analysis. A total of 131 genes were found to increase or decrease 1.5-fold or higher in response to 17 beta-estradiol (1 nM for 48 h). Besides, the gene regulation occuring in steroid-deprived conditions showed that 17Î²-HSD1 modulates gene expression in steroid-independent manners. Our study thus demonstrates that 17Î²-HSD1 modulates the E2-independent transcription of endogenous genes in T47D cells. The E2-dependent transcription as well as the E2-independent transcription are significantly modulated by 17Î²-HSD1 in breast cancer cells We first report here that breast cancer cell transcript profile is independtly modulated by both 17Î²-HSD1 and its principale product estradiol. Microarrays was used to study the effect of 17Î²-HSD1 gene knockdown on gene expression and on endogenous ERG in T47D cells. The sense and antisense sequences of three 17Î²-HSD1 siRNAs were selected and synthesized. Scramble siRNA was used as control siRNA. Two days before transfection, T47D cells in T75 were cultured in steroid deprived medium. On the transfection day, cells in T75 flasks were trypsined and ressuspended in a fresh charcoal-treated medium. Cells were then reverse-transfected with 17Î²-HSD1 specific siRNAs or with negative control siRNA.Two days (48 hours) after transfection, cell culture media were replaced by fresh charcoal-treated medium containing either the steroid E2 (1 nM) or ethanol as a vehicle control, and cells were incubated for two more days before RNA extraction.

Dataset Information

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

Publications

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.

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