Reprimo, a potential p53-dependent tumor suppressor gene, is frequently hypermethylated in estrogen receptor α-positive breast cancer

Kurt Buchegger, Ismael Riquelme, Tamara Viscarra, Carmen Ili, Priscilla Brebi, Tim Hui Ming Huang, Juan Carlos Roa

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Aberrant DNA methylation is a hallmark of many cancers. Currently, there are four intrinsic molecular subtypes in breast cancer (BC): Luminal A, B, Her2-positive, and triple negative (TNBC). Recently, The Cancer Genome Atlas (TCGA) project has revealed that Luminal subtypes have higher levels of genome-wide methylation that may be a result of Estrogen/Estrogen receptor α (E2/ERα) signaling pathway activation. In this study, we analyze promoter CpG-island (CGIs) of the Reprimo (RPRM) gene in breast cancers (n = 77), cell lines (n = 38), and normal breast tissue (n = 10) using a MBDCap-seq database. Then, a validation cohort (n = 26) was used to confirm the results found in the MBDCap-seq platform. A differential methylation pattern was found between BC and cell lines compared to normal breast tissue. In BC, a higher DNA methylation was observed in tissues that were ERα-positive than in ERα-negative ones; more precisely, subtypes Luminal A compared to TNBC. Also, significant reverse correlation was observed between DNA methylation and RPRM mRNA expression in BC. Our data suggest that ERα expression in BC may affect the DNA methylation of CGIs in the RPRM gene. This approach suggests that DNA methylation status in CGIs of some tumor suppressor genes could be driven by E2 availability, subsequently inducing the activation of the ERα pathway.

Original languageEnglish (US)
Article number1525
JournalInternational journal of molecular sciences
Volume18
Issue number8
DOIs
StatePublished - Aug 15 2017

Keywords

  • Breast cancer
  • DNA methylation
  • Estrogen
  • Estrogen receptor α
  • Reprimo

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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