University of Louisville
DHEA Stimulates miR-21 Expression in Breast Cancer Cells
Institution
University of Louisville
Faculty Advisor/ Mentor
Carolyn Klinge
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.
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.