THE INSULIN RECEPTOR ON NORMAL AND DIABETIC MAMMARY RAT TUMORIGENESIS

ALICIA GUTIÉRREZ; LORENA SAMBUCO; MÁXIMO CROCI; GABRIELA MARTÍN; MARIEL NÚÑEZ; ELENA RIVERA; ANDREA RANDI; ROSA BERGOC

Villa Carlos Paz, Córdoba, Argentina

Congreso; XLIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2008

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Several studies report that insulin hormone and its receptor (IR) may be associated to an increased risk for a number of malignancies. We demonstrated that N-Nitroso-N-methylurea (NMU) induced mammary adenocarcinomas in normal rats and more differentiated lesions in diabetic ones. The aim of the present study was to investigate the expression and localization of IR in mammary tissue during the carcinogenic process as well in mammary tumors, in both diabetic and non diabetic rats. Carcinomas were induced in animals by NMU injection to 50, 80 and 110 days old rats. Diabetes was induced by streptozotocin administration at 36 h of animals life. Breast tissue specimens were processed at 60, 90 and 120 days, as well as samples from developed tumors. Immunohistochemical analysis and Western blot were performed. Receptor expression was markedly increased in NMU-mammary glands (+++) vs. normal ones (-/+). In diabetic rats, IR expression was similar to normal glands (+), whilst in diabetic NMU-injected animals the expression was scarce (+/++). All tumors developed in non-diabetic rats presented high undifferentiated grade, cribriform pattern and marked IR expression (++++); tumors developed in diabetic animals showed differentiated pattern, low malignant grade and slight IR expression (+/++). Results suggest a correlation between IR expression and degree of differentiation on mammary tumors.