Defining the genomic signature of the parous breast.
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.
Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Suraj
S
Peri
Ricardo López
RL
de Cicco
Julia
J
Santucci-Pereira
Michael
M
Slifker
Eric A
EA
Ross
Irma H
IH
Russo
Patricia A
PA
Russo
Alan A
AA
Arslan
Ilana
I
Belitskaya-Lévy
Anne
A
Zeleniuch-Jacquotte
Pal
P
Bordas
Per
P
Lenner
Janet
J
Åhman
Yelena
Y
Afanasyeva
Robert
R
Johansson
Fathima
F
Sheriff
Göran
G
Hallmans
Paolo
P
Toniolo
Jose
J
Russo
D000368:Aged; D001940:Breast / Q000378:metabolism*; D016000:Cluster Analysis; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016612:Paraffin Embedding; D010298:Parity / Q000235:genetics*; D011247:Pregnancy; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
C483080:CCNL2 protein, human; D016213:Cyclins; D014157:Transcription Factors