Sex Steroids Regulate Expression of Genes Containing Long Interspersed Elements-1s in Breast Cancer Cells

Abstract

Long interspersed elements-1s (LINE-1s) are dispersed all over the human genome. There is evidence that hypomethylation of LINE-1s and levels of sex steroids regulate gene expression leading to cancer development. Here, we compared mRNA levels of genes containing an intragenic LINE-1 in breast cancer cells treated with various sex steroids from Gene Expression Omnibus (GEO), with the gene expression database using chi-square analysis (http//www.ncbi.nlm.nih.gov/geo). We evaluated whether sex steroids in uence expression of genes containing an intragenic LINE-1. Three sex steroids at various concentrations, 1 and 10 nM estradiol (E2), 10 nM progesterone (PG) and 10 nM androgen (AN), were assessed. In breast cancer cells treated with 1 or 10 nM E2, a signi cant percentage of genes containing an intragenic LINE-1 were down-regulated. A highly signi cant percentage of E2-regulated genes containing an intragenic LINE-1 was down-regulated in cells treated with 1 nM E2 for 3 hours (<3.70E-25; OR1.91; 95% CI2.16-1.69). Similarly, high percentages of PG or AN- regulated genes containing an intragenic LINE-1 wwere also down-regulated in cells treated with 10 nM PG or 10 nM AN for 16 hr (p9.53E-06; OR1.65; 95% CI2.06-1.32 and p3.81E-14; OR2.01; 95% CI2.42-1.67). Interestingly, a signi cant percentage of AN-regulated genes containing an intragenic LINE-1 was up-regulated in cells treated with 10 nM AN for 16 hr (p4.03E-02; OR1.40; 95% CI1.95-1.01). These ndings suggest that intragenic LINE-1s may play roles in sex steroid mediated gene expression in breast cancer cells, which could have signi cant implications for the development and progression of sex steroid-dependent cancers.