TRANSCRIPTION OF THE PRORENIN GENE IN NORMAL AND DISEASED BREAST

The angiotensin II type 1 (AT1) receptor is present in a wide variety of human and animal tissues, and is particularly abundant in epithelia l cells. Because of this, and because it is known that tissue renin an giotensin systems (RASs) exist that have specific local functions, we investigated the expression and localisation of components of the RAS in normal and diseased breast tissue. Using a monoclonal antibody to t he AT1 receptor, immunocytochemistry confirmed that the AT1 receptor w as characteristically distributed in ductal epithelial cells in both n ormal and malignant tissue, and in most, although not all, cells in in vasive tumours. Transcription of prorenin mRNA was studied by in situ hybridisation, using a DIG-ddUTP tail-labelled probe specific for the human prorenin gene. In normal tissue, and in cases of ductal carcinom a in situ, prorenin mRNA was distributed in myoepithelial cells and in a band of connective tissue cells completely surrounding the AT1-cont aining ductal epithelial cells. This prorenin transcribing tissue was disrupted and attenuated in invasive tumours, and in some of these, pr orenin mRNA transcription could not be detected at all. Functions ascr ibed to the tissue RASs include regulation of mitosis and tissue model ling, as well as fluid and electrolyte transport. The results presente d here strongly suggest the possibility that a tissue RAS may also be present in the breast, closely coupled to the provision of angiotensin II to the AT1 receptors in ductal epithelial cells. This mechanism is disrupted in cancer. (C) 1998 Elsevier Science Ltd. All rights reserv ed.