University of Louisville

DHEA Stimulates miR-21 Expression in Breast Cancer Cells

Presenter Information

Jacob Bell, University of Louisville

Institution

University of Louisville

Abstract

MicroRNAs (miRNAs) regulate the expression of genes at the post transcriptional level by inhibiting the translation of messenger RNAs (mRNAs) into protein and/or stimulating their degradation. miR-21 is an oncomiR that is overexpressed in various cancers including breast cancer. miR-21 expression in MCF-7 human breast cancer cells is suppressed by estradiol (E2). In postmenopausal women, breast cancer growth is stimulated by non-ovarian estrogen sources including dehydroepiandrosterone (DHEA), an adrenal androgen that is metabolized into androgens and estrogens. The goal of the research was to determine if and how DHEA regulates miR-21 levels in breast cancer cells including estrogen receptor  (ER-positive and negative cell lines and endocrine-sensitive and resistant cell lines. Breast cancer cells were treated with various concentrations of DHEA, DHEA metabolites or E2. DHEA increased miR-21 expression in certain ER+ cell lines; however, the DHEA induction in T47D cells was not inhibited by ICI, an antiestrogen, suggesting that DHEA operated through a non ER-mediated mechanism. E2 induced miR-21 in T47D and MDA-MB-231 cells. Since MDA-MB-231 cells are ER-negative, the mechanism for E2-induced miR-21 is unknown. The DHEA metabolite 3β-adiol increased miR-21 expression in MDA-MB-231 cells that were co-treated with ICI. Because DHEA is a precursor to androgens, DHEA metabolites activate AR-mediated miR-21 transcription. Western blots examined AR expression in MCF-7 and HepG2 hepatic cells. HepG2 expressed AR but MCF-7 did not, which indicates that that DHEA must operate though a non AR-mediated pathway(s) in MCF-7. Further studies are needed to dissect DHEA’s effect on miR-21 in breast cancer.

This document is currently not available here.

Share

COinS
 

DHEA Stimulates miR-21 Expression in Breast Cancer Cells

MicroRNAs (miRNAs) regulate the expression of genes at the post transcriptional level by inhibiting the translation of messenger RNAs (mRNAs) into protein and/or stimulating their degradation. miR-21 is an oncomiR that is overexpressed in various cancers including breast cancer. miR-21 expression in MCF-7 human breast cancer cells is suppressed by estradiol (E2). In postmenopausal women, breast cancer growth is stimulated by non-ovarian estrogen sources including dehydroepiandrosterone (DHEA), an adrenal androgen that is metabolized into androgens and estrogens. The goal of the research was to determine if and how DHEA regulates miR-21 levels in breast cancer cells including estrogen receptor  (ER-positive and negative cell lines and endocrine-sensitive and resistant cell lines. Breast cancer cells were treated with various concentrations of DHEA, DHEA metabolites or E2. DHEA increased miR-21 expression in certain ER+ cell lines; however, the DHEA induction in T47D cells was not inhibited by ICI, an antiestrogen, suggesting that DHEA operated through a non ER-mediated mechanism. E2 induced miR-21 in T47D and MDA-MB-231 cells. Since MDA-MB-231 cells are ER-negative, the mechanism for E2-induced miR-21 is unknown. The DHEA metabolite 3β-adiol increased miR-21 expression in MDA-MB-231 cells that were co-treated with ICI. Because DHEA is a precursor to androgens, DHEA metabolites activate AR-mediated miR-21 transcription. Western blots examined AR expression in MCF-7 and HepG2 hepatic cells. HepG2 expressed AR but MCF-7 did not, which indicates that that DHEA must operate though a non AR-mediated pathway(s) in MCF-7. Further studies are needed to dissect DHEA’s effect on miR-21 in breast cancer.