Open Access Highly Accessed Research article

Defining the genomic signature of the parous breast

Suraj Peri1, Ricardo López de Cicco2, Julia Santucci-Pereira2, Michael Slifker1, Eric A Ross1, Irma H Russo2, Patricia A Russo2, Alan A Arslan34, Ilana Belitskaya-Lévy5, Anne Zeleniuch-Jacquotte4, Pal Bordas67, Per Lenner7, Janet Åhman6, Yelena Afanasyeva4, Robert Johansson8, Fathima Sheriff2, Göran Hallmans8, Paolo Toniolo349 and Jose Russo2*

Author Affiliations

1 Department of Biostatistics and Bioinformatics, Philadelphia, PA, 19111, USA

2 Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA 19111, USA

3 Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, 10016, USA

4 Division of Epidemiology, New York University School of Medicine, New York, NY, 10016, USA

5 Division of Biostatistics, Department of Environmental Medicine, New York University School of Medicine, New York, NY, 10016, USA

6 Sunderby Hospital, Luleå and the Norrbotten Mammography Screening Program, Luleå, Sweden

7 Departments of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden

8 Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

9 Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

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BMC Medical Genomics 2012, 5:46  doi:10.1186/1755-8794-5-46

Published: 11 October 2012

Abstract

Background

It is accepted that a woman's lifetime risk of developing breast cancer after menopause is reduced by early full term pregnancy and multiparity. This phenomenon is thought to be associated with the development and differentiation of the breast during pregnancy.

Methods

In order to understand the underlying molecular mechanisms of pregnancy induced breast cancer protection, we profiled and compared the transcriptomes of normal breast tissue biopsies from 71 parous (P) and 42 nulliparous (NP) healthy postmenopausal women using Affymetrix Human Genome U133 Plus 2.0 arrays. To validate the results, we performed real time PCR and immunohistochemistry.

Results

We identified 305 differentially expressed probesets (208 distinct genes). Of these, 267 probesets were up- and 38 down-regulated in parous breast samples; bioinformatics analysis using gene ontology enrichment revealed that up-regulated genes in the parous breast represented biological processes involving differentiation and development, anchoring of epithelial cells to the basement membrane, hemidesmosome and cell-substrate junction assembly, mRNA and RNA metabolic processes and RNA splicing machinery. The down-regulated genes represented biological processes that comprised cell proliferation, regulation of IGF-like growth factor receptor signaling, somatic stem cell maintenance, muscle cell differentiation and apoptosis.

Conclusions

This study suggests that the differentiation of the breast imprints a genomic signature that is centered in the mRNA processing reactome. These findings indicate that pregnancy may induce a safeguard mechanism at post-transcriptional level that maintains the fidelity of the transcriptional process.

Keywords:
Gene expression profiling; Pregnancy; Breast morphology; Breast differentiation; Parous and nulliparous breast transcriptome; Breast cancer risk; Normal breast transcriptome; Bioinformatics.