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Santucci-Pereira J , Zeleniuch-Jacquotte A , Afanasyeva Y , Zhong H , Slifker M , Peri S , Ross EA , Lopez de Cicco R , Zhai Y , Nguyen T , Sheriff F , Russo IH , Su Y , Arslan AA , Bordas P , Lenner P , Ahman J , Landstrom Eriksson AS , Johansson R , Hallmans G , Toniolo P , Russo J
Genomic signature of parity in the breast of premenopausal women
Breast Cancer Res. 2019 Mar 28;21(1) :46
PMID: 30922380    PMCID: PMC6438043    URL: https://www.ncbi.nlm.nih.gov/pubmed/30922380
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BACKGROUND: Full-term pregnancy (FTP) at an early age confers long-term protection against breast cancer. Previously, we reported that a FTP imprints a specific gene expression profile in the breast of postmenopausal women. Herein, we evaluated gene expression changes induced by parity in the breast of premenopausal women. METHODS: Gene expression profiling of normal breast tissue from 30 nulliparous (NP) and 79 parous (P) premenopausal volunteers was performed using Affymetrix microarrays. In addition to a discovery/validation analysis, we conducted an analysis of gene expression differences in P vs. NP women as a function of time since last FTP. Finally, a laser capture microdissection substudy was performed to compare the gene expression profile in the whole breast biopsy with that in the epithelial and stromal tissues. RESULTS: Discovery/validation analysis identified 43 differentially expressed genes in P vs. NP breast. Analysis of expression as a function of time since FTP revealed 286 differentially expressed genes (238 up- and 48 downregulated) comparing all P vs. all NP, and/or P women whose last FTP was less than 5 years before biopsy vs. all NP women. The upregulated genes showed three expression patterns: (1) transient: genes upregulated after FTP but whose expression levels returned to NP levels. These genes were mainly related to immune response, specifically activation of T cells. (2) Long-term changing: genes upregulated following FTP, whose expression levels decreased with increasing time since FTP but did not return to NP levels. These were related to immune response and development. (3) Long-term constant: genes that remained upregulated in parous compared to nulliparous breast, independently of time since FTP. These were mainly involved in development/cell differentiation processes, and also chromatin remodeling. Lastly, we found that the gene expression in whole tissue was a weighted average of the expression in epithelial and stromal tissues. CONCLUSIONS: Genes transiently activated by FTP may have a role in protecting the mammary gland against neoplastically transformed cells through activation of T cells. Furthermore, chromatin remodeling and cell differentiation, represented by the genes that are maintained upregulated long after the FTP, may be responsible for the lasting preventive effect against breast cancer.
1465-542x Santucci-Pereira, Julia ORCID: http://orcid.org/0000-0003-4958-1128 Zeleniuch-Jacquotte, Anne Afanasyeva, Yelena Zhong, Hua Slifker, Michael Peri, Suraj Ross, Eric A Lopez de Cicco, Ricardo Zhai, Yubo Nguyen, Theresa Sheriff, Fathima Russo, Irma H Su, Yanrong Arslan, Alan A Bordas, Pal Lenner, Per Ahman, Janet Landstrom Eriksson, Anna Stina Johansson, Robert Hallmans, Goran Toniolo, Paolo Russo, Jose grant 02-2010-117/Avon Foundation for Women P30-CA006927/National Cancer Institute Journal Article England Breast Cancer Res. 2019 Mar 28;21(1):46. doi: 10.1186/s13058-019-1128-x.