Role of Progesterone Receptors in Mammary Development and Carcinogenesis

摘要

It is well established that signaling through estrogen and progesterone through then-cognate receptors, estrogen receptor alpha (ERalpha) and progesterone receptor (PR) are essential for both the development of mammary glands and their transformation to preneoplastic and neoplastic counterparts. Several years ago it was demonstrated that both mouse and human mammary epithelial cells proliferate in response to progesterone (1-3). Despite this, among the two ovarian steroids, estrogens have been traditionally associated with an increased risk for breast cancer. In recent years, several studies, including our own, provide compelling evidence that progesterone/PR signaling may play a crucial role in the transformation of mammary epithelial cells. The identity of a particular cell is established during development and conversion of a normal cell to its malignant counterpart is accompanied by alterations in certain fundamental mechanisms that define its identity. Accordingly, to identify the mechanisms that trigger carcinogenesis, it is essential to understand the processes that ensure normal development and maintenance of this phenotype. This chapter summarizes our studies on PR during normal mammary development and their relevance to carcinogenesis.