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21.12.2016 | Original Article

Systematic Investigation of Expression of G2/M Transition Genes Reveals CDC25 Alteration in Nonfunctioning Pituitary Adenomas

verfasst von: Henriett Butz, Kinga Németh, Dóra Czenke, István Likó, Sándor Czirják, Vladimir Zivkovic, Kornélia Baghy, Márta Korbonits, Ilona Kovalszky, Péter Igaz, Károly Rácz, Attila Patócs

Erschienen in: Pathology & Oncology Research | Ausgabe 3/2017

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Abstract

Dysregulation of G1/S checkpoint of cell cycle has been reported in pituitary adenomas. In addition, our previous finding showing that deregulation of Wee1 kinase by microRNAs together with other studies demonstrating alteration of G2/M transition in nonfunctioning pituitary adenomas (NFPAs) suggest that G2/M transition may also be important in pituitary tumorigenesis. To systematically study the expression of members of the G2/M transition in NFPAs and to investigate potential microRNA (miRNA) involvement. Totally, 80 NFPA and 14 normal pituitary (NP) tissues were examined. Expression of 46 genes encoding members of the G2/M transition was profiled on 34 NFPA and 10 NP samples on TaqMan Low Density Array. Expression of CDC25A and two miRNAs targeting CDC25A were validated by individual quantitative real time PCR using TaqMan assays. Protein expression of CDC25A, CDC25C, CDK1 and phospho-CDK1 (Tyr-15) was investigated on tissue microarray and immunohistochemistry. Several genes’ expression alteration were observed in NFPA compared to normal tissues by transcription profiling. On protein level CDC25A and both the total and the phospho-CDK1 were overexpressed in adenoma tissues. CDC25A correlated with nuclear localized CDK1 (nCDK1) and with tumor size and nCDK1 with Ki-67 index. Comparing primary vs. recurrent adenomas we found that Ki-67 proliferation index was higher and phospho-CDK1 (inactive form) was downregulated in recurrent tumors compared to primary adenomas. Investigating the potential causes behind CDC25A overexpression we could not find copy number variation at the coding region nor expression alteration of CDC25A regulating transcription factors however CDC25A targeting miRNAs were downregulated in NFPA and negatively correlated with CDC25A expression. Our results suggest that among alterations of G2/M transition of the cell cycle, overexpression of the CDK1 and CDC25A may have a role in the pathogenesis of the NFPA and that CDC25A is potentially regulated by miRNAs.

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Titel: Systematic Investigation of Expression of G2/M Transition Genes Reveals CDC25 Alteration in Nonfunctioning Pituitary Adenomas
verfasst von: Henriett Butz
Kinga Németh
Dóra Czenke
István Likó
Sándor Czirják
Vladimir Zivkovic
Kornélia Baghy
Márta Korbonits
Ilona Kovalszky
Péter Igaz
Károly Rácz
Attila Patócs
Publikationsdatum: 21.12.2016
Verlag: Springer Netherlands
Erschienen in: Pathology & Oncology Research / Ausgabe 3/2017
Print ISSN: 1219-4956
Elektronische ISSN: 1532-2807
DOI: https://doi.org/10.1007/s12253-016-0163-5

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16.04.2024 | Maligne primäre ZNS-Tumoren | Nachrichten

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Systematic Investigation of Expression of G2/M Transition Genes Reveals CDC25 Alteration in Nonfunctioning Pituitary Adenomas

Abstract

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Abstract

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