Journal Article

Defining the genomic signature of the parous breast

Slifker, Michael, Lenner, Per, Belitskaya-Lévy, Ilana, Ross, Eric A, Bordas, Pal, Åhman, Janet, Peri, Suraj, Toniolo, Paolo, Afanasyeva, Yelena, Johansson, Robert, Hallmans, Göran, Sheriff, Fathima, Russo, Irma H, Russo, Jose, de Cicco, Ricardo López, Russo, Patricia A, Arslan, Alan A, Santucci-Pereira, Julia, Zeleniuch-Jacquotte, Anne

2012

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aged / Bioinformatics / Biomedical and Life Sciences / Biomedicine / Breast - metabolism / Breast cancer / Breast cancer risk / Breast differentiation / Breast morphology / Cancer / Cell differentiation / Cluster Analysis / Comparative analysis / Complications and side effects / Cyclins - genetics / Cyclins - metabolism / Development and progression / Down-Regulation - genetics / Female / Gene Expression / Gene Expression Profiling / Genes / Genetic aspects / Genetic transcription / Genome, Human - genetics / Genomes / Genomics / Health aspects / Hormone replacement therapy / Human Genetics / Humans / Immunohistochemistry / Medical research / Menopause / Microarrays / Middle Aged / Normal breast transcriptome / Oligonucleotide Array Sequence Analysis / Paraffin Embedding / Parity - genetics / Parous and nulliparous breast transcriptome / Postmenopausal women / Pregnancy / Prevention / Reproducibility of Results / Research Article / Reverse Transcriptase Polymerase Chain Reaction / Risk factors / RNA / Stem cells / Studies / Transcription Factors - genetics / Transcription Factors - metabolism / Transcriptome - genetics / Up-Regulation - genetics / Women / Womens health