The expression of syndecan-1, syndecan-4 and decorin in healthy human breast tissue during the menstrual cycle

In order to unravel the interactions between the epithelium and the extra cellular matrix (ECM) in breast tissue progressing to cancer, it is necessary to understand the relevant interactions in healthy tissue under normal physiologic settings. Proteoglycans in the ECM play an important role in the signaling between the different tissue compartments. The proteoglycan decorin is abundant in the breast stroma. Decreased expression in breast cancer tissue is a sign of a poor tumor prognosis. The heparane sulphate proteoglycans syndecan-1 and syndecan-4 promote the integration of cellular adhesion and proliferation. The aim of this study was to investigate the gene expression and location of decorin, syndecan-1 and syndecan-4 in the healthy breast during the menstrual cycle.

Tissue from healthy women undergoing breast reduction plastic surgery was examined using immunohistochemistry (n = 38) and Real-Time RT-PCR (n = 20). Both parous and nulliparous women were eligible and the mean age of the women was 34(+/- 10 years) with regular menstrual cycles (28 +/- 7 days). None of the women had used hormonal treatment the last three months. The women were randomized to needle biopsy two months before the operation in the follicular or luteal menstrual phase and for another biopsy at the operation in the opposite phase. Serum samples were obtained to characterize the menstrual phase. The Wilcoxon signed rank test and Mann Whitney test were used for statistical analyses.

By real time-RT-PCR the gene signal for all three proteoglycans; decorin (p = 0.02) and syndecan-1 (p = 0.03) and syndecan-4 (p = 0.02) was significantly lower among parous women in the luteal phase than in the follicular phase. Immunohistochemistry confirmed the identification of the proteins but no significant difference between menstrual phases was observed. Serum samples verified the menstrual phase.

Our study shows, for the first time in the healthy breast, a significantly lower expression of the genes for the three proteoglycans, decorin, syndecan-1 and syndecan-4 in the luteal phase during the menstrual cycle. These changes were registered under normal physiologic conditions. Since ECM molecules appear to be involved in tumor progression, these findings in the normal breast could constitute a base for further studies in women receiving hormonal therapy or those with breast cancer.