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 alpha (RARalpha), epigenetically regulates in a concerted fashion the transcription of two RA-responsive genes, the RA receptor beta2 (RARbeta2) and the cellular retinol-binding protein 1 (CRBP1). Specifically, an impaired RA signal through RARalpha in human breast epithelial cells triggers a repressive epigenetic domino effect, involving first RARbeta2 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 RARbeta2 and second CRBP1. The identification of this epigenetic network mechanistically linking RARbeta2 and CRBP1 transcription provides the basis for devising more accurate epigenetic tests for the prediction of breast cancer risk.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Bistulfi G,Pozzi S,Ren M,Rossetti S,Sacchi Ndoi
10.1158/0008-5472.CAN-06-1052subject
Has Abstractpub_date
2006-11-01 00:00:00pages
10308-14issue
21eissn
0008-5472issn
1538-7445pii
66/21/10308journal_volume
66pub_type
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