Journal of Neuro-Oncology

, Volume 55, Issue 3, pp 149–158

Alterations of INK4ap16—p14ARF/INK4bp15 Expression and Telomerase Activation in Meningioma Progression

  • Matthias Simon
  • Tjoung-Won Park
  • Gertraud Köster
  • Ralph Mahlberg
  • Matthias Hackenbroch
  • Jan Boström
  • Thomas Löning
  • Johannes Schramm
Article

DOI: 10.1023/A:1013863630293

Cite this article as:
Simon, M., Park, TW., Köster, G. et al. J Neurooncol (2001) 55: 149. doi:10.1023/A:1013863630293
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Abstract

Dysregulation of cell cycle progression and telomerase activation have been implicated in malignant tumor progression as well as in the evasion of senescence and immortalization. We have investigated expression of the cell cycle control and tumor suppressor genes INK4ap16–p14ARF, INK4bp15–p10 and RB, and their relation to telomerase activation during malignant meningioma progression. 7/26 (27%) benign, 3/12 (25%) atypical but 4/7 (57%) anaplastic tumors lacked both, p16 and p15 protein expression. 14/39 (36%) benign and atypical but 5/7 (71%) anaplastic meningiomas contained no p14ARF mRNA. 2/46 (4%) tumors failed to express pRB. We observed frequent differential loss of expression of the alternatively spliced INK4a tumor suppressors p16 and p14ARF. Exclusive expression of the alternative INK4b transcript p10 possibly at the expense of p15 and therefore resulting in loss of p15 tumor suppressor activity was noted in two meningiomas. We have previously described telomerase activity or expression of the telomerase catalytic subunit hTERT in this meningioma series. Telomerase activation was detected in 10/27 (37%) benign, but 18/19 (95%) non-benign meningiomas. We observed no significant overall correlation between loss of INK4a/INK4b expression and telomerase activation. In conclusion, our results suggest a greater role for losses of INK4a/INK4b gene products in meningioma formation and malignant progression than previously thought. Inactivation of p16/p15- and p14ARF-dependent pathways possibly in conjunction with telomerase activation might be critical steps for a meningioma cell towards escape from senescence, that is, immortalization.

meningioma progression p16 p15 p14ARF p10 telomerase 

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Matthias Simon
    • 1
  • Tjoung-Won Park
    • 2
  • Gertraud Köster
    • 1
  • Ralph Mahlberg
    • 1
  • Matthias Hackenbroch
    • 1
  • Jan Boström
    • 1
  • Thomas Löning
    • 3
  • Johannes Schramm
    • 1
  1. 1.Neurochirurgische UniversitätsklinikGermany
  2. 2.UniversitätsfrauenklinikBonnGermany
  3. 3.Abt. für GynäkopathologieUniversität HamburgHamburgGermany

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