Parity induces a specific genomic signature in the human breast

4062 We have postulated that the lifetime protective effect of an early pregnancy against breast cancer is due to the complete differentiation of the mammary gland, which results in the replacement of the Stem cell 1 that is a component of the nulliparous breast epithelium with a new stem cell, called Stem cell 2, which is characterized by a specific genomic signature (Russo J &Russo IH., Endocrine Related Cancer 4:7, 1997). For demonstrating this hypothesis we compared the genomic profile of the epithelium and the stroma of normal breast tissues from reduction mammoplasties performed in three postmenopausal nulliparous and five postmenopausal parous women. The epithelium and the stroma were separately dissected using laser capture microdissection (LCM) and the RNA of each compartment and each sample was isolated, amplified using PCR methodology, and hybridized to cDNA glass-microarrays containing 40,000 genes, placing in the green channel (Cy3) the human reference RNA and in the red channel (Cy5) the breast tissue samples. Data were analyzed employing the GeneSight software version 4.2 after Lowess normalization eliminating all the outlier spots with Flags 1 to 5. Using the Confidence analysis with 99% level we select only the genes differentiate expressed between same tissue compartments in each group, selecting a cut off of ± 2.0 log up-or down-respect to the reference (p