Genomic signature of parity in the breast of premenopausal women

Autor: Janet Åhman, Suraj Peri, Paolo Toniolo, Pál Bordás, Julia Santucci-Pereira, Theresa D. Nguyen, Ricardo Lopez de Cicco, Robert Johansson, Fathima Sheriff, Anna Stina Landström Eriksson, Jose Russo, Michael Slifker, Irma H. Russo, Per Lenner, Göran Hallmans, Eric A. Ross, Yubo Zhai, Hua Zhong, Alan A. Arslan, Anne Zeleniuch-Jacquotte, Yelena Afanasyeva, Yanrong Su
Rok vydání: 2019
Předmět:
Parous and nulliparous breast transcriptome
Breast differentiation
Stromal cell
Cellular differentiation
Biology
lcsh:RC254-282
Chromatin remodeling
Andrology
03 medical and health sciences
0302 clinical medicine
Breast cancer
Pregnancy
Gene expression
medicine
Humans
Immune response
Mammary Glands
Human
Gene
Normal breast transcriptome
Medicinsk genetik
Laser capture microdissection
Cancer och onkologi
Gene Expression Profiling
Computational Biology
Reproducibility of Results
Genomics
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Immunohistochemistry
Gene expression profiling
Parity
Gene Ontology
Gene Expression Regulation
Premenopause
Cancer and Oncology
030220 oncology & carcinogenesis
Female
Transcriptome
Breast cancer risk
Medical Genetics
Biomarkers
Signal Transduction
Research Article
Zdroj: Breast Cancer Research : BCR
Breast Cancer Research, Vol 21, Iss 1, Pp 1-19 (2019)
ISSN: 1465-542X
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s13058-019-1128-x) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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