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Endocrine and reproductive influences significantly affect play major roles in the lifetime risk steadily increasing incidence of breast cancer development in women.. Nulliparity is one of the most firmly established risk factors for breast cancer, whereas early full term pregnancy and parity confer a significant protection. In order to elucidate the molecular pathways through which pregnancy exerts a protective effect, we have analyzed the genomic profile of lobules type 1 (Lob 1) present in reduction mammoplasty specimens obtained from 5 parous and 2 nulliparous postmenopausal women. Total RNA was obtained from epithelial cells and from the stroma of Lob 1 that were dissected using laser capture microdisection (LCM). RNAs were individually amplified employing oligo-DT T7 primer and in vitro transcription reaction. The breast epithelium amplified RNA and a human universal reference RNA were hybridized to a cDNA glass microarray containing 40,000 features. Using the confidence analysis with 99% level changes observed we selected only the genes differentially expressed between same tissue compartments in each group, selecting a cut-off detected a cluster of ±2.0 log up or down respect to the reference (p<0.01). Gene transcripts with genes related to immune- surveillance function that were significantly up-regulated in the epithelium but not in the stroma of consistently and significantly in the parous women's epithelial cells. In order to expand these observations, in the present works we performed real time RT-PCR using a microfluidic card platform. The TaqMan® Low Density Immune Profiling Array contained 90 genes related to the immune system, and 18S rRNA as an internal control (Applied Biosystems 7900HT TaqMan® Low Density Array Upgrade, ABI). Epithelial cells from parous women significantly (p<0.001) 20 genes related to immune surveillance when compared with the RNA obtained from nulliparous women. Those genes included: BCL2-associated X protein (BAX), complement component 3 (C3), chemokine (C-C motif), receptor 4 (CXCR4), CD34 antigen, Collagen IV (COL4A5), glucuronidase beta (GUSB), interleukin 1 β (IL-1β), interleukin 6 (IL6), major histocompatibility complex class II, DR α (HLA-DRA), signal transducer and activator of transcription 3 (STAT3) and CD34 antigen (CD34), among others. The observed activation of immune surveillance genes in the breast epithelial cells of postmenopausal parous women leads us to postulate that suggest that changes induced by an early pregnancy has permanently have changed its the genomic signature, of the cells making them more easily recognized by the immune surveillance system if they are exposed to able to be protected from toxic carcinogenic or agents or carcinogens, by eliciting and early immune surveillance of the transformed cells. (This work was supported by NIH-NCI grant RO1-CA093599 from the National Cancer Institute).

[Proc Amer Assoc Cancer Res, Volume 47, 2006]