TY - JOUR ID - 69903 TI - PAX6 Promoter Methylation Correlates with MDA-MB-231 Cell Migration, and Expression of MMP2 and MMP9 JO - Asian Pacific Journal of Cancer Prevention JA - APJCP LA - en SN - 1513-7368 AU - Urrutia, Guillermo AU - Laurito, Sergio AU - Campoy, Emanuel AU - Nasif, Daniela AU - Branham, María Teresita AU - Roqué, María AD - IHEM, National University of Cuyo, CONICET, Mendoza, Argentina. AD - IHEM, National University of Cuyo, CONICET, Faculty of Exact and Natural Sciences, Mendoza, Argentina. AD - IHEM, National University of Cuyo, CONICET, Faculty of Medical Sciences, Mendoza, Argentina. Y1 - 2018 PY - 2018 VL - 19 IS - 10 SP - 2859 EP - 2866 KW - breast cancer KW - Metastasis KW - DNA Methylation KW - PAX6 KW - Matrix Metalloproteinases DO - 10.22034/APJCP.2018.19.10.2859 N2 - Objective: Breast cancer is a heterogeneous disease characterized by an accumulation of genetic and epigeneticalterations that lead tumor cells to acquire characteristics like the capacity for invasion and metastasis. Metastasisremains a major challenge in cancer management and understanding of its molecular basis should result in improvedprevention, diagnosis, and treatment of breast cancer patients. The aim of this study was to investigate how promoterDNA methylation regulates PAX6 gene expression and influences breast carcinoma cell migration. Methods: PAX6promoter methylation was detected by Methyl Specific-Multiplex Ligation Probe Amplification (MS-MLPA). Geneexpression was evaluated using qRT-PCR, while the effect of PAX6 on migration was ssessed by wound healing assay.In addition, MMP2 and MMP9 genes were studied using different bioinformatic tools. Results: The PAX6 promoter ismethylated in breast cancer cell lines and methylation in this region impacts on its expression. Migration assays revealedthat PAX6 overexpression promotes cell migration, while PAX6 inhibition decreases it. More importantly, we foundthat migration is affected by PAX6 methylation status. Employing bioinformatic analysis, binding sites for PAX6 onthe regulatory regions of the MMP2 and MMP9 genes were established, PAX6 overexpression increasing MMP2 andMMP9 expression at the mRNA level. Conclusion: Our study provides novel insights into epigenetic events that regulatePAX6 expression and molecular mechanisms by which PAX6 modifies the migration capacity of breast cancer cells. UR - https://journal.waocp.org/article_69903.html L1 - https://journal.waocp.org/article_69903_1459356ca0bf062e32e822d1a247d04c.pdf ER -