Investigation of molecular mechanisms in nonfunctioning pituitary adenomas

The molecular mechanism of nonfunctioning pituitary adenoma (NFA) formation is still unknown. In this study, I have investigated the relationship between NFA and functional pituitary adenomas and expression of mRNA and proteins which are involved in cell cycle and DNA damage control mechanisms. In this study, I analyzed p16, Rb, pRb-S608, E2F1, pE2F1-S364, p73, CyclinD1 protein and mRNA expression in twenty acromegaly, twenty Cushing's disease and twenty-seven NFA patients with immunohistochemistry, western blotting, and qRT-PCR. The results were statistically evaluated with the clinical and histopathological findings of the patients. Cyclin D1 mRNA expression and Rb protein expression were high in NFA. In addition, whereas E2F1 and pE2F1-S364 protein expression levels were high, p16 mRNA and protein expression were low in NFA. In the Cushing group, CHEK2 mRNA expression and p16 mRNA and protein expression were high while E2F1, pE2F1-S364 and p73 protein expression levels were low. In acromegaly, expression of CHEK2 mRNA, Rb protein and Cyclin D1 mRNA was low, while pE2F1-S364 and p73 protein expression levels were high. This is the first demonstration of the relationship between E2F1, pE2F1-S364, CHEK2 and p73 mRNA and protein expression levels involved in adenoma formation in NFA, Cushing, and Acromegaly patients. The results of this study will help to elucidate the molecular mechanisms underlying pathogenesis of pituitary adenomas and will contribute for the development of new approaches in the treatment and prevention of disease. Keywords: Nonfunctioning pituitary adenoma, pE2F1-S364, E2F1, CHEK2, p73