Abstract

1019 Background: The protective effect of an early first full-term pregnancy (FFTP) in relation to breast cancer risk is well known, but the molecular and cell-specific mechanisms involved remain unclear. Methods: We analysed the global gene expression profiles of normal mammary tissues taken from a matched multiparous and nulliparous woman using Serial analysis of Gene Expression (SAGE) and Generation of longer cDNA fragments from SAGE tags for Gene Identification. Results: The differentiation markers such as caseinκ, caseinβ, keratin14 en CCAAT/enhancer binding protein β and δ are increased after pregnancy. Genes like bullous pemphigoïd antigen 1, decorin, vimentin, retinoid acid receptor responder, and the transcription factor early growth response 1 are also candidate markers for a pregnancy-induced differentiation. Histon deacetylase 2, Calpain, CAXII, collagen 1, osteonectin and connective tissue growth factor are decreased after pregnancy. Several of the genes that are lost after pregnancy encoded cytoskeletal and extra cellular matrix proteins. One of such genes, the small breast epithelial mucin (SBEM), consists most probably of a secreted sialoglycoprotein and may show a cancer-associated expression. SBEM is almost completely down regulated upon a FTTP but is expressed in 96 % of breast tumor cells. At least three tags corresponding to new genes show expression differences similar to SBEM. Conclusions: Our SAGE data found a different gene expression profile after pregnancy. Some of these genes might be useful in breast cancer risk assessment. No significant financial relationships to disclose.

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