The present work was aimed to determine the genomic signature between the undifferentiated lobule type 1 (Lob 1) of the nulliparous women's breast, and the well differentiated lobule type 3 (Lob 3) of the parous women's breast. This study was performed using the RNA obtained from primary cultures of Lob 1 from 3 nulliparous women and Lob 3 of 3 parous pre-menopausal women, and hybridized to cDNA array membranes that contain 1,176 human genes (Clontech Human Cancer 1,2 array). Lob 3 has a gene expression profile significantly different from that of Lob 1. Lob 3 showed 47 genes differentially expressed (>5-fold) when compared with those in Lob 1. Among these genes, RhoE gene is amplified 9.44- fold in the Lob 3 of the parous breast. Other genes such as protein tyrosine phosphatase (PPTPCAAX1 or PRL-1), insulin-like growth factor binding protein-3 (IGFBP-3) and lipocalin 2, are also over expressed in Lob 3 of pre menopausal women. We have confirmed the differential expression of a number of genes using semi- quantitative RT-PCR and immunocytochemical methods. The results indicate that differentially expressed genes occur during normal human breast lobular differentiation and these changes might persistently modify the genomic signature of the breast epithelia.

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