MicroRNA molecules (miRNAs) have important roles in regulating cell behavior. In addition, their expression levels can be used in tumor classification. The expression of miRNAs has been to be regulated by the androgen receptor (AR), which seems to play an interesting role in the tumorigenic process of breast cancer. We hypothesized that AR may control the behavior of breast cancer cells via modulating the expression of miRNAs. Using PCR arrays, we examined the differential expression of 84 miRNAs in three breast cancer cell lines, the luminal MCF-7 and T47D cells and the molecular apocrine MDA-MB-453 cells. Each cell line had distinct miRNA expression with let-7a and -7b as markers of the MDA-MB-453 cells, and miR-205 as a marker for the luminal cell lines. Treatment of the cells with the AR agonist, CI-4AS-1, resulted in dissimilar alterations in miRNA expression among the three cell lines. CI-4AS-1 reduced the expression let-7a, let-7d, and miR-205-5p in the MDA-MB-453 cells. These three molecules are known to block epithelial-to-mesenchymal transition (EMT) and, interestingly, their reduction paralleled a dramatic morphological alteration of the molecular apocrine cells into fibroblast-like shape. The expression of two other miRNAs, miR-100-5p and miR-125-5p, was also decreased. These two molecules have previously been shown to down-regulate the expression of the metalloprotease-13 (MMP-13), which was up-regulated in the MDA-MB-453 cells following AR activation. Collectively, these data indicate that miRNA molecules can differentiate breast cancer cells and that AR may control the biological behavior of breast cancer cells and protein expression via regulating the expression of miRNAs.
Presenting Author: Mamoun Ahram, Department of Physiology and Biochemistry, Faculty of Medicine, The University of Jordan, Amman 11942, Jordan. Email: email@example.com.