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P27/CDKN1B Translational Regulators in Pituitary Tumorigenesis

C S Martins1, R C Camargo2, F P Saggioro3

  • 1Department of Internal Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo, Brazil.

Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme
|November 9, 2016
PubMed

Insights

Pituitary tumors show decreased P27 protein, but this is not due to changes in key translational regulators like DKC1 or RPS13. Further research into DKC1 variants is warranted for pituitary tumor development insights.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • P27 (CDKN1B) protein is frequently underexpressed in pituitary tumors.
  • The underlying mechanisms, particularly translational regulation, require further investigation.

Purpose of the Study:

  • To investigate whether translational regulation contributes to P27 (CDKN1B) underexpression in pituitary adenomas.
  • To evaluate the expression of P27 targets and key translational regulators (DKC1, RPS13, miR221, miR222).
  • To screen for DKC1 gene variants in pituitary adenomas.

Main Methods:

  • Gene and protein expression analysis (RT-PCR, immunohistochemistry) of P27/CDKN1B, CCNE1, CDK2, DKC1, RPS13, miR221, and miR222 in 48 pituitary adenomas and 7 normal pituitaries.
  • Sequencing of all 15 exons of the DKC1 gene.
  • In silico analysis of identified DKC1 variants.

Main Results:

  • P27 protein underexpression was confirmed across all pituitary adenoma subtypes.
  • CCNE1 mRNA was overexpressed in nonfunctioning pituitary adenomas (NFPA), but not at the protein level.
  • No significant differential gene expression was found for RPS13, DKC1, miR221, or miR222 among the groups.
  • Frequent DKC1 single nucleotide polymorphisms (SNPs) were observed, along with rare variants in 11% of tumors, though in silico analysis suggested no deleterious effects.

Conclusions:

  • P27 protein underexpression in pituitary adenomas is confirmed, likely involving post-translational mechanisms.
  • The expression of P27 translational regulators (DKC1, RPS13, miR221, miR222) does not explain P27 underexpression.
  • DKC1 variants are prevalent in pituitary adenomas but their direct role in tumorigenesis remains unclear.

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