The role of secreted frizzled-related protein in parity-induced protection against breast cancer.

B135

Breast cancer is the most frequent cancer in women and represents the second leading cause of cancer death among women. It is essential understand the mechanistic actions by which breast cancer occurs and how it can be prevented. Parity induced hormonal changes decrease the risk of breast cancer development in both humans and mice and recent data suggests that pregnancy levels of ovarian hormones regulate the changes in hundreds of genes. One gene in particular, secreted frizzled-related protein (sFRP), has piqued our interest for several reasons. Members of this protein family are implicated in antagonizing the Wnt signaling pathway, which is known for its involvement in development as well as in the pathogenesis of various types of tumours, including breast cancer. We sought to determine whether the increase in sFRP expression in response to pregnancy levels of ovarian hormones is a persistent change. Five weeks following pregnancy, we found that the expression level of sFRP is higher in parous mice when compared with nulliparous mice. Interestingly, although sFRP is abundantly expressed in normal breast tissue, its expression is lost in about 70% of breast cancer specimens. Furthermore, sFRP is not detected breast carcinoma cell lines. Therefore, we generated an sFRP expressing MDA-MB-231 breast cancer cell line to determine whether sFRP altered the proliferation or the death rate of these cells. Although 3H-Thymidine assays revealed that sFRP does not affect cell proliferation, FACS analysis revealed that there is a significant increase in cell death when MDA-MB-231 cells express sFRP. Taken together, these data suggest that sFRP may play a role in the observed protective effect of parity by maintaining the appropriate apoptotic cellular response that is normally lost in breast tumours.