The role of GABA-ergic system in human mammary gland pathology and in growth of transplantable murine mammary cancer

In this paper we described the results of our studies on the baclophen (gam ma aminobutyric acid (GABA)-B receptor agonist) inhibitory effect on the gr owth of experimental mammary cancer 16/C in mice and on the estimation of G ABA level and GAD (glutamine acid decarboxylase - the key enzyme in GABA sy nthesis) activity after this treatment in mice. The experimental data are c onfronted with the estimation of GABA level and GAD activity in human mamma ry gland material taken from the patients with benign breast tumors of diff erent pathological and age related hormonal stages. A significant inhibitio n of 16/C tumor growth in treated with baclophen mice was observed. Mean GA BA level and GAD activity were significantly higher both in tumor and in no rmal tissue of baclophen treated mice in comparison to control animals. The results of clinical studies have shown that the lowest GABA level and GAD activity in tumor and normal mammary gland tissue was detected in patients in peri-menopausal stage. Both, in human and mouse material, the GABA level and GAD activity were higher in tumor than in normal tissue and there was a clear positive correlation between GABA level and GAD activity in both ti ssues studied. GABA level and GAD activity in tumor and in normal tissue we re lower in patients with dysplasia than in patients with fibroadenoma. Con sidering our results, namely an inhibitory effect of GABA receptor agonist on mammary cancer growth and the correlation between GABA level and the sta ge of bt east pathology and/or hormonal activity, it seems probable that GA BA-ergic system is involved in hormonal regulation and pathogenesis of brea st cancer.