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Genomic signature of parity in the breast of premenopausal women.

Abstract：

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.

journal_name

Breast Cancer Res

journal_title

Breast cancer research : BCR

authors

Santucci-Pereira J,Zeleniuch-Jacquotte A,Afanasyeva Y,Zhong H,Slifker M,Peri S,Ross EA,López de Cicco R,Zhai Y,Nguyen T,Sheriff F,Russo IH,Su Y,Arslan AA,Bordas P,Lenner P,Åhman J,Landström Eriksson AS,Johansson R,H

doi

10.1186/s13058-019-1128-x

subject

Has Abstract

pub_date

2019-03-28 00:00:00

pages

issue

eissn

1465-5411

issn

1465-542X

pii

10.1186/s13058-019-1128-x

journal_volume

pub_type

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Genomic signature of parity in the breast of premenopausal women.