mTOR is Frequently Active in GH-Secreting Pituitary Adenomas without Influencing their Morphopathological Features
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mTOR is Frequently Active in GH-Secreting Pituitary Adenomas without Influencing their Morphopathological Features Emir Ahmed Sajjad & Grzegorz Zieliński & Maria Maksymowicz & Łukasz Hutnik & Tomasz Bednarczuk & Paweł Włodarski Published online: 8 January 2013 # Springer Science+Business Media New York 2013
Abstract Initiating factors and mechanisms of tumor formation are poorly understood in nonfamilial pituitary adenomas. Alteration of intracellular pathways is an underlying event in numerous neoplasms. Among them, excessive activation of mammalian target of rapamycin (mTOR) pathway and its two main regulators, Akt and Erk, has been detected frequently in solid tumors. This study tests the activation of mTOR pathway in pituitary adenomas and its influence on their morphopathological features. Fifty-three pituitary adenomas were fresh frozen after surgery and analyzed by western blotting using phospho-specific antibodies. The impact of Akt and Erk activation on mTOR pathway was assessed in five primary cultures derived from the excised adenomas using selective kinase inhibitors. Statistical correlations of size, volume, Ki-67 %, Knosp’s Electronic supplementary material The online version of this article (doi:10.1007/s12022-012-9230-y) contains supplementary material, which is available to authorized users.
grading, and somatostatin receptor (SSTR) expression with the activation of mentioned kinases was performed. GHomas showed the highest frequency (71 %) and level of mTOR pathway activity comparing to other adenomas (33 %). No significant correlation was found between mTOR activation and any of the morphopathological features in the studied samples. mTOR kinase phosphorylation was independent of Erk and Akt in primary cultures. Erk activity was significant in all types of adenomas but was the highest in control samples. Its phosphorylation correlated inversely with the Knosp’s grading in nonfunctional pituitary adenomas and directly with somatostatin receptor subtype 2 A expression in GHomas. Presented data point to the noteworthy mTOR activity in GHomas. However, the lack of correlation with morphopathological features, its independence of Erk and Akt phosphorylation, and high level of Erk activity in control pituitary necessitate further research for clarifying the role of these pathways in pituitary adenomas.
E. A. Sajjad : Ł. Hutnik : P. Włodarski (*) Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, Chałubińskiego 5, 02-004 Warszawa, Poland e-mail: [email protected]
Keywords Pituitary adenoma . mTOR . Erk . Akt . Immunohistochemistry
G. Zieliński Department of Neurosurgery, Military Institute of Medicine, Szaserów 128, 04-141 Warszawa, Poland
Pituitary adenomas (PAs) are a diverse group of benign tumors arising from the anterior pituitary gland. They are the third most common intracranial neoplasms after meningiomas and gliomas, accounting for approximately 15 % of all intracranial tumors [1]. PAs are grossly characterized by their hormonal
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