Parathyroid Hormone Related Protein (PTHrP) Regulates Estrogen Receptor Expression
Parathyroid hormone related protein (PTHrP) is required for specification of the mammary mesenchyme during embryonic development. In WT mice, the mammary mesenchyme consists of 3-4 layers of stromal cells that express ER. Overexpression of PTHrP in the basal layer of the epidermis, results in ectopic ER expression in the ventral dermis. Conversely, loss of PTHrP results in ablation of ER expression. Deletion of Wnt pathway components such as beta-catenin also abolishes ER expression. These data suggest that PTHrP-induced Wnt signaling regulates ER expression.
To determine if PTHrP similarly mediates ER expression in breast cancer and bone, we used RNA harvested from osteoblasts treated with PTHrP. Semi-quantitative PCR was used to analyze ER gene expression and to demonstrate that PTHrP treatment results in a 2-fold increase in the levels of ER. We also used immunofluoresence to demonstrate that treatment of T47D breast cancer cells with PTHrP increases ER levels.
Taken together, out studies demonstrate that PTHrP regulates ER expression in bone and breast and that PTHrP could be used as a therapeutic agent to in the treatment of postmenopausal osteoporosis and ER-negative breast cancer.