ANGIOTENSIN-II TYPE-1 RECEPTOR EXPRESSION IN HUMAN BREAST TISSUES

We demonstrate the expression of angiotensin II type 1 (AT1) receptors in normal and diseased human breast tissues. Using monoclonal antibod y 6313/G2, directed against a specific sequence in the extracellular d omain of the AT1 receptor, immunocytochemical analysis revealed positi ve immunoreactivity in membrane and cytoplasm of specific cell types. Immunoblotting of solubilized proteins separated by sodium dodecyl sul phate polyacrylamide gel electrophoresis (SDS-PAGE) from benign and ma lignant tumours identified a single immunoreactive species with a mole cular mass of approximately 60 kDa, consistent with that of the mature glycosylated receptor. In studies of [I-125]angiotensin II binding us ing breast membrane preparations, concentrations of specific angiotens in II binding sites were found to range from 1.8 to 100 fmol mg(-1) pr otein, with a K-d of approximately 60 nM. Most of the specifically bou nd [I-125]angiotensin II was displaced by losartan, a specific angiote nsin II type 1 receptor antagonist, while less was displaced by the AT 2 receptor type antagonist, CGP42112A, thus confirming the prevalence of AT1 receptors in this tissue type, These data suggest that the reni n-angiotensin system may be involved in normal and abnormal breast tis sue function.