Abstract A31: Reprimo, a potential tumor suppressor gene TP53-dependent, modulates negatively cell migration and invasion in the MDA-MB-231 breast cancer cell line

Abstract

Abstract Background: Reprimo, a highly glycosylated protein, is a new downstream effector of p53-induced cell cycle arrest at the G2/M checkpoint, and a putative tumor suppressor gene frequently silenced via methylation of its promoter region in several malignances. The aim of this study was to characterize the epigenetic inactivation and its biological function in BC cell lines. Methods: The correlation between Reprimo methylation and loss of mRNA expression was assessed in six breast cancer cell lines by methylation specific PCR (MSP), 5-Aza-2′-deoxycytidine treatment and qRT-PCR assays. MDA-MB-231 cells were chosen to investigate the phenotypic effect of Reprimo in cell proliferation, cell cycle, cell death, cell migration and invasion. Results: In the cancer methylome system (CMS) (web-based system for visualizing and analyzing genome-wide methylation data of human cancers), the CpG island region of RPRM (1,1Kb) was hypermethylated in breast cancer compared to normal breast tissue. Downregulation of RPRM mRNA by methylation was confirmed in MDA-MB-231 and BT-20 cell lines. In addition, overexpression of RPRM in MDA-MB-231 cells resulted in decreased rates of cell migration, wound healing and invasion in vitro (P < 0.0001). However, RPRM overexpression did not alter cell viability, rate of death cell and G2/M cell cycle transition in this biological model. Conclusion: Taken together, these data suggest that RPRM is involved in decreased cell migration and invasion in vitro, acting as a potential tumor suppressor gene in the MDA-MB-231 cell line. Citation Format: Kurt Buchegger, Tamara Viscarra, Carmen Gloria Ili, Ismael Riquelme, Pablo Letelier, Alejandro Corvalan, Priscilla Brebi, Tim Hui-Ming Huang, Juan Carlos Roa. Reprimo, a potential tumor suppressor gene TP53-dependent, modulates negatively cell migration and invasion in the MDA-MB-231 breast cancer cell line. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Cancer Cell Cycle - Tumor Progression and Therapeutic Response; Feb 28-Mar 2, 2016; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(11_Suppl):Abstract nr A31.