| mTOR is Frequently Active in GH-Secreting Pituitary Adenomas without Influencing their Morphopathological Features. | |
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MedLine Citation:
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PMID: 23296986 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Emir Ahmed Sajjad; Grzegorz Zieliński; Maria Maksymowicz; Lukasz Hutnik; Tomasz Bednarczuk; Paweł Włodarski |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-8 |
Journal Detail:
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Title: Endocrine pathology Volume: - ISSN: 1559-0097 ISO Abbreviation: Endocr. Pathol. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9009288 Medline TA: Endocr Pathol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, Chałubińskiego 5, 02-004, Warszawa, Poland. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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