naa a22 4500 510773265 CHVBK 20180411083221.0 cr unu---uuuuu 180411e20130301xx s 000 0 eng 10.1007/s12022-012-9230-y doi (NATIONALLICENCE)springer-10.1007/s12022-012-9230-y mTOR is Frequently Active in GH-Secreting Pituitary Adenomas without Influencing their Morphopathological Features [Elektronische Daten] [Emir Sajjad, Grzegorz Zieliński, Maria Maksymowicz, Łukasz Hutnik, Tomasz Bednarczuk, Paweł Włodarski] 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 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. Springer Science+Business Media New York, 2013 Pituitary adenoma nationallicence mTOR nationallicence Erk nationallicence Akt nationallicence Immunohistochemistry nationallicence Sajjad Emir Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, Chałubińskiego 5, 02-004, Warszawa, Poland aut Zieliński Grzegorz Department of Neurosurgery, Military Institute of Medicine, Szaserów 128, 04-141, Warszawa, Poland aut Maksymowicz Maria Department of Pathology, Maria Skłodowska-Curie Institute of Oncology, Roentgena 5, 02-781, Warszawa, Poland aut Hutnik Łukasz Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, Chałubińskiego 5, 02-004, Warszawa, Poland aut Bednarczuk Tomasz Department of Internal Disease and Endocrinology, Medical University of Warsaw, Banacha 1A, 02-097, Warszawa, Poland aut Włodarski Paweł Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, Chałubińskiego 5, 02-004, Warszawa, Poland aut Endocrine Pathology Springer US; http://www.springer-ny.com 24/1(2013-03-01), 11-19 1046-3976 24:1<11 2013 24 12022 https://doi.org/10.1007/s12022-012-9230-y text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12022-012-9230-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Sajjad Emir Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, Chałubińskiego 5, 02-004, Warszawa, Poland aut NATIONALLICENCE 700 1- Zieliński Grzegorz Department of Neurosurgery, Military Institute of Medicine, Szaserów 128, 04-141, Warszawa, Poland aut NATIONALLICENCE 700 1- Maksymowicz Maria Department of Pathology, Maria Skłodowska-Curie Institute of Oncology, Roentgena 5, 02-781, Warszawa, Poland aut NATIONALLICENCE 700 1- Hutnik Łukasz Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, Chałubińskiego 5, 02-004, Warszawa, Poland aut NATIONALLICENCE 700 1- Bednarczuk Tomasz Department of Internal Disease and Endocrinology, Medical University of Warsaw, Banacha 1A, 02-097, Warszawa, Poland aut NATIONALLICENCE 700 1- Włodarski Paweł Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, Chałubińskiego 5, 02-004, Warszawa, Poland aut NATIONALLICENCE 773 0- Endocrine Pathology Springer US; http://www.springer-ny.com 24/1(2013-03-01), 11-19 1046-3976 24:1<11 2013 24 12022 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer