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

  • Chaiwongwatanakul, Saichon (Department of Biological Sciences, Faculty of Science, Chulalongkorn University) ;
  • Yanatatsaneejit, Pattamawadee (Human Genetics Research Group, department of Botany, Faculty of Sciences, Chulalongkorn University) ;
  • Tongsima, Sissades (Biostatistics and Informatics Laboratory, Genome Institute, National Center for Genetic Engineering and Biotechnology) ;
  • Mutirangura, Apiwat (Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University) ;
  • Boonyaratanakornkit, Viroj (Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University)
  • Published : 2016.08.01

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 influence 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 significant percentage of genes containing an intragenic LINE-1 were down-regulated. A highly significant percentage of E2-regulated genes containing an intragenic LINE-1 was down-regulated in cells treated with 1 nM E2 for 3 hours (p<3.70E-25; OR=1.91; 95% CI=2.16-1.69). 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 (p=9.53E-06; OR=1.65; 95% CI=2.06-1.32 and p=3.81E-14; OR=2.01; 95% CI=2.42-1.67). Interestingly, a significant percentage of AN-regulated genes containing an intragenic LINE-1 was up-regulated in cells treated with 10 nM AN for 16 hr (p=4.03E-02; OR=1.40; 95% CI=1.95-1.01). These findings suggest that intragenic LINE-1s may play roles in sex steroid mediated gene expression in breast cancer cells, which could have significant implications for the development and progression of sex steroid-dependent cancers.

Keywords

Estrogen;progesterone;androgen;LINE-1s;gene experession;breast cancer cells

Acknowledgement

Supported by : Thailand Graduate Institute of Science and Technology (TGIST), National Science and Technology Development Agency (NSTDA), Chulalongkorn University

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