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Hormones

, Volume 11, Issue 3, pp 297–307 | Cite as

Oncogene-induced senescence in pituitary adenomas and carcinomas

  • Krystallenia I. Alexandraki
  • Mohammed Munayem Khan
  • Harvinder S. Chahal
  • Nadezhda S. Dalantaeva
  • Giampaolo Trivellin
  • Dan M. Berney
  • Philippe Caron
  • Vera Popovic
  • Marija Pfeifer
  • Suzanne Jordan
  • Márta Korbonits
  • Ashley B. Grossman
Research paper

Abstract

OBJECTIVE

The model of ‘oncogene-induced senescence’ (OIS), resulting in cell-proliferation arrest, has recently been suggested as a possible explanation for the non-progression of pituitary tumours to malignancy. The aim of the study was to compare the expression of β-galactosidase as a molecular marker of OIS, and p21/p16 as additional markers involved in mediating OIS, in pituitary adenomas, carcinomas and normal pituitary tissue.

DESIGN

We performed: a) semi-quantitative immunohistochemistry (β-galactosidase, p16, p21) in 41 pituitary adenomas [(11 GH-secreting, 9 PRL-secreting, 10 ACTH-secreting, 11 non-functioning (NFPAs)], 6 carcinomas (3 multihormonal: PRL/ACTH/GH, PRL/ACTH, PRL/GH/FSH; 1 non-functioning; 2 ACTH-secreting) and 7 normal pituitary tissues; b) quantitative PCR of mRNA (p16 and p21) in 6 GH-secreting, 6 NFPAs and 6 normal pituitary tissues.

RESULTS

β-galactosidase was significantly increased in GH-secreting tumours (P=0.002), NFPAs (P=0.04), macroadenomas (P=0.03) and carcinomas (P=0.02), as compared to normal pituitary tissue. We found that p16 expression was significantly lower in all tumours (both adenomas and carcinomas) probably secondary to reduced transcription, at least for NFPAs; p21 showed a different biological behaviour, implying that p21 and p16 may play different roles in the senescence of each individual type of adenoma.

CONCLUSIONS

β-galactosidase was significantly over-expressed in GH-secreting and NFPAs, and unexpectedly also in carcinomas. We speculate that the senescence pathway, which may explain the rarity of malignant progression to carcinomas in GH-secreting and NFPAs, might not be universal but cell-type specific.

Key words

p-galactosidase Pituitary adenoma Pituitary carcinoma p16 p21 Senescence 

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Copyright information

© Hellenic Endocrine Society 2012

Authors and Affiliations

  • Krystallenia I. Alexandraki
    • 1
  • Mohammed Munayem Khan
    • 1
  • Harvinder S. Chahal
    • 1
  • Nadezhda S. Dalantaeva
    • 1
  • Giampaolo Trivellin
    • 1
  • Dan M. Berney
    • 2
  • Philippe Caron
    • 3
  • Vera Popovic
    • 4
  • Marija Pfeifer
    • 5
  • Suzanne Jordan
    • 2
  • Márta Korbonits
    • 1
  • Ashley B. Grossman
    • 1
  1. 1.Centre for EndocrinologyWilliam Harvey Research InstituteUK
  2. 2.Department of HistopathologyBarts and the London School of MedicineLondonUK
  3. 3.Department of Endocrinology and Metabolic diseasesCHU LarreyToulouseFrance
  4. 4.Neuroendocrine Unit, Endocrinology ClinicUniversity Clinical CenterBelgradeUK
  5. 5.Department of Endocrinology, Diabetes and Metabolic DiseasesUniversity Medical Centre LjubljanaLjubljanaSlovenia

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