Reprimo as a modulator of cell migration and invasion in the MDA-MB-231 breast cancer cell line

Kurt Buchegger, Carmen Ili, Ismael Riquelme, Pablo Letelier, Alejandro H. Corvalán, Priscilla Brebi, Hui-ming Huang, Juan Carlos Roa

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background: Reprimo (RPRM), 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 RPRM 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 RT-PCR assays. MDA-MB-231 cells were chosen to investigate the phenotypic effect of RPRM 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 (1.1 kb) was hypermethylated in breast cancer compared to normal breast tissue; more interesting still was that ERaα(+) tumors showed higher methylation intensity than ERaα(-). 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. However, RPRM overexpression did not alter cell viability, phosphatidylserine (PS) translocation or G2/M cell cycle transition. 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.

Original languageEnglish (US)
JournalBiological Research
DOIs
StateAccepted/In press - Jan 22 2016

Keywords

  • Invasion
  • MDA-MB-231
  • Migration
  • Reprimo

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Buchegger, K., Ili, C., Riquelme, I., Letelier, P., Corvalán, A. H., Brebi, P., Huang, H., & Roa, J. C. (Accepted/In press). Reprimo as a modulator of cell migration and invasion in the MDA-MB-231 breast cancer cell line. Biological Research. https://doi.org/10.1186/s40659-016-0066-7