Glutamyl- but Not Aspartyl- Aminopeptidase Activity is Modified in Serum of N-Methyl Nitrosourea-induced Rat Mammary Tumours

Background: The rat model of breast cancer induced by the administration of N-methyl-nitrosourea (NMU) constitutes a useful tool for dissecting the initiation, promotion and progression process of carcinogenesis. Angiogenesis, the recruitment of new blood vessels, is an essential component of the metastatic pathway. Tumour vessels have an aberrant response to constrictor hormones, such as angiotensin II (Ang II). Ang II degradation to form angiotensin III (Ang III) begins with the action of glutamyl aminopeptidase (GluAP) and aspartyl aminopeptidase (AspAP), named together as aminopeptidase A activity (APA). The present work analyses GluAP and AspAP activities in serum of NMU-induced rat mammary tumours, to evaluate the putative value of these activities as biological markers of the initiation and promotion of the disease. Materials and Methods: Serum AspAP and GluAP activities were measured fluorimetrically using their corresponding aminoacyl-β-naphthylamide. Results: The increase found in GluAP but not in AspAP suggests an increase in Ang III and a decrease in Ang II serum circulating levels. Conclusion: The decrease in Ang II may be responsible for the overexpression of AT 1 receptors described in breast cancer. However, increased levels of Ang III, which exhibit the same affinity for the AT 1 receptor, would favour the development of the disease.