Defining the genomic signature of the parous breast

BMC Medical Genomics

Jose Russo⁷  Paolo Toniolo⁵  Göran Hallmans¹  Fathima Sheriff⁷  Robert Johansson¹  Yelena Afanasyeva⁸  Janet Åhman⁶  Per Lenner³  Pal Bordas³  Anne Zeleniuch-Jacquotte⁸  Ilana Belitskaya-Lévy⁴  Alan A Arslan⁸  Patricia A Russo⁷  Irma H Russo⁷  Eric A Ross²  Michael Slifker²  Julia Santucci-Pereira⁷  Ricardo López de Cicco⁷  Suraj Peri² 

[1] Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden;Department of Biostatistics and Bioinformatics, Philadelphia, PA, 19111, USA;Departments of Radiation Sciences and Oncology, Umeå University, Umeå, Sweden;Division of Biostatistics, Department of Environmental Medicine, New York University School of Medicine, New York, NY, 10016, USA;Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland;Sunderby Hospital, Luleå and the Norrbotten Mammography Screening Program, Luleå, Sweden;Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA 19111, USA;Division of Epidemiology, New York University School of Medicine, New York, NY, 10016, USA

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

Others  :  1134584
DOI  :  10.1186/1755-8794-5-46

 received in 2012-01-24, accepted in 2012-09-19,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Peri et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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