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Analysis of Cell Cycle Position in Mammalian Cells
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Systematic Investigation of Expression of G2/M Transition Genes Reveals CDC25 Alteration in Nonfunctioning Pituitary

Henriett Butz1, Kinga Németh2, Dóra Czenke2

  • 1Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, 46 Szentkirályi str, Budapest, H-1088, Hungary. butz.henriett@med.semmelweis-univ.hu.

Pathology Oncology Research : POR
|December 23, 2016
PubMed

Insights

Overexpression of cell cycle regulators CDC25A and CDK1 may drive nonfunctioning pituitary adenomas (NFPA). Downregulated microRNAs targeting CDC25A suggest a potential regulatory mechanism in pituitary tumor development.

Area of Science:

  • Endocrinology and Oncology
  • Cell Cycle Regulation
  • Molecular Biology

Background:

  • Cell cycle dysregulation, particularly G1/S checkpoint, is implicated in pituitary adenomas.
  • Alterations in G2/M cell cycle transition are observed in nonfunctioning pituitary adenomas (NFPAs).
  • MicroRNA (miRNA) deregulation of Wee1 kinase suggests miRNA involvement in pituitary tumorigenesis.

Purpose of the Study:

  • To systematically analyze G2/M cell cycle transition gene expression in NFPAs.
  • To investigate the potential role of microRNAs in regulating these genes.
  • To explore the protein expression of key G2/M regulators in NFPA pathogenesis.

Main Methods:

  • Gene expression profiling of 46 G2/M transition genes using TaqMan Low Density Array on 34 NFPAs and 10 normal pituitaries.
  • Quantitative real-time PCR validation for CDC25A and its targeting miRNAs.
  • Tissue microarray and immunohistochemistry to assess protein expression of CDC25A, CDC25C, CDK1, and phospho-CDK1.

Main Results:

  • Significant alterations in several G2/M transition genes were observed in NFPAs compared to normal tissues.
  • Overexpression of CDC25A and both total and phospho-CDK1 proteins in adenoma tissues.
  • Downregulation of CDC25A-targeting miRNAs in NFPAs, correlating negatively with CDC25A expression.

Conclusions:

  • Overexpression of CDK1 and CDC25A are potential contributors to nonfunctioning pituitary adenoma pathogenesis.
  • CDC25A overexpression may be regulated by downregulated microRNAs in NFPAs.
  • Recurrent adenomas show higher proliferation (Ki-67) and lower inactive phospho-CDK1.
Keywords:
CDC25ACell cycleG2/M transitionPituitary adenomamiRNA

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