Parathyroid hormone-related protein: a developmental regulatory molecule necessary for mammary gland development

Parathyroid hormone-related protein (PTHrP) was originally identified as the tumor factor responsible for a clinical syndrome known as humoral hypercalcemia of malignancy. It is now appreciated that PTHrP3 is a developmental regulatory molecule expressed during the formation of a wide variety of organs. Recently, our laboratory has demonstrated that PTHrP is necessary for mammary gland development. Our studies have suggested that this molecule participates in the regulation of epithelial-mesenchymal interactions during embryonic mammary development and perhaps also during adolescent ductal morphogenesis. In addition, it has been suggested that PTHrP plays a critical role in the establishment of bone metastases in breast cancer. In this article, we will discuss the current knowledge of the mechanisms underlying PTHrPs actions during normal mammary development and in breast cancer.