ANGIOTENSIN-CONVERTING ENZYME AND ENKEPHALINASE IN HUMAN BREAST CYST FLUID

Palpable breast cysts with an apocrine epithelial lining (type 1) are reported to be associated with a higher risk of developing breast canc er. The composition of breast cyst fluid (BCF) might include those fac tors involved in this increased risk. In this study peptidase activiti es that were active against the substrate [I-125]metenkephalin-Arg-Phe were detected in BCF. The products were identified by reversed phase high-performance liquid chromatography (HPLC) as [I-125]Tyr-Gly-Gly an d [I-125]Met-enkephalin. This proteolysis was not inhibited by PCMB, p epstatin A, leupeptin or aprotinin but was by EDTA, showing that the a ctivity was due to metalloproteases. The production of [I-125]Try-Gly- Gly was inhibited by phosphoramidon and thiorphan, whereas that of [I- 125]met-enkephalin was inhibited by captopril and Bothrops jararaca pe ptide, indicating that these activities are enkephalinase and angioten sin-converting enzyme (ACE) respectively. A fluorometric assay for ACE demonstrated that ACE levels are significantly higher in type 2 BCF t han in type 1 BCF (30.8 vs 6.1 nmol hr(-1) 10 mu l(-1), P<0.001). As t he increased risk of cancer is linked to type 1 cysts it is possible t hat higher levels of peptidase in type 2 BCF reflect a protective envi ronment in the breast in which mitogenic peptide growth factors are ne utralised by proteolysis.