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Russo J , Santucci-Pereira J , de Cicco RL , Sheriff F , Russo PA , Peri S , Slifker M , Ross E , Mello MLS , Vidal BC , Belitskaya-Levy I , Arslan A , Zeleniuch-Jacquotte A , Bordas P , Lenner P , Ahman J , Afanasyeva Y , Hallmans G , Toniolo P , Russo IH
Pregnancy-induced chromatin remodeling in the breast of postmenopausal women
International Journal of Cancer. 2012 Sep;131(5) :1059-1070
PMID: WOS:000305756900033    PMCID: PMC3350833   
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Early pregnancy and multiparity are known to reduce the risk of women to develop breast cancer at menopause. Based on the knowledge that the differentiation of the breast induced by the hormones of pregnancy plays a major role in this protection, this work was performed with the purpose of identifying what differentiation-associated molecular changes persist in the breast until menopause. Core needle biopsies (CNB) obtained from the breast of 42 nulliparous (NP) and 71 parous (P) postmenopausal women were analyzed in morphology, immunocytochemistry and gene expression. Whereas in the NP breast, nuclei of epithelial cells were large and euchromatic, in the P breast they were small and hyperchromatic, showing strong methylation of histone 3 at lysine 9 and 27. Transcriptomic analysis performed using Affymetrix HG_U133 oligonucleotide arrays revealed that in CNB of the P breast, there were 267 upregulated probesets that comprised genes controlling chromatin organization, transcription regulation, splicing machinery, mRNA processing and noncoding elements including XIST. We concluded that the differentiation process induced by pregnancy is centered in chromatin remodeling and in the mRNA processing reactome, both of which emerge as important regulatory pathways. These are indicative of a safeguard step that maintains the fidelity of the transcription process, becoming the ultimate mechanism mediating the protection of the breast conferred by full-term pregnancy.
Russo, Jose Santucci-Pereira, Julia de Cicco, Ricardo Lopez Sheriff, Fathima Russo, Patricia A. Peri, Suraj Slifker, Michael Ross, Eric Mello, Maria Luiza S. Vidal, Benedicto C. Belitskaya-Levy, Ilana Arslan, Alan Zeleniuch-Jacquotte, Anne Bordas, Pal Lenner, Per Ahman, Janet Afanasyeva, Yelena Hallmans, Goran Toniolo, Paolo Russo, Irma H. Avon Foundation[02-2008-034]; National Institutes of Health[CA006927]; Sao Paulo State Research Foundation[06/0066-8] Grant sponsor: Avon Foundation (Women Breast Cancer Research Program); Grant number: 02-2008-034; Grant sponsor: National Institutes of Health; Grant number: CA006927; Grant sponsor: Sao Paulo State Research Foundation (Carl Zeiss/Kontron equipment); Grant number: FAPESP, no. 06/0066-8 49 Wiley-blackwell Hoboken 965gz