A repressive epigenetic domino effect confers susceptibility to breast epithelial cell transformation: Implications for predicting breast cancer risk

Gala Bistulfi, Silvia Pozzi, Ming Qiang Ren, Stefano Rossetti, Nicoletta Sacchi

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Retinoic acid (RA) is a master epigenetic regulator that plays a pivotal role in both breast morphogenesis and development. Here, we show for the first time that RA, via the RA receptor α (RARα), epigenetically regulates in a concerted fashion the transcription of two RA-responsive genes, the RA receptor α2 (RARβ2) and the cellular retinol-binding protein 1 (CRBP1). Specifically, an impaired RA signal through RARα in human breast epithelial cells triggers a repressive epigenetic domino effect, involving first RARβS and second CRBP1. The phenotype acquired by breast epithelial cells clearly implies that the resistance to RA-mediated growth inhibition precedes the acquisition of morphological epithelial transformation, thus supporting the occurrence of sequential transcriptional silencing of first RARβ2 and second CRBP1. The identification of this epigenetic network mechanistically linking RARβ2 and CRBP1 transcription provides the basis for devising more accurate epigenetic tests for the prediction of breast cancer risk.

Original languageEnglish (US)
Pages (from-to)10308-10314
Number of pages7
JournalCancer Research
Volume66
Issue number21
DOIs
Publication statusPublished - Nov 1 2006

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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