mTOR Pathway As a Potential Target In a Subset of Human Medulloblastoma

Tímea Pócza, A. Sebestyén, Eszter Turányi, T. Krenács, Ágnes Márk, Tamás Béla Sticz, Zsuzsanna Jakab, P. Hauser

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

As mammalian Target of Rapamycin (mTOR) plays role in protein synthesis and metabolism, mTOR pathway activation is involved in the pathogenesis of several types of tumors. Our aim was to elucidate its role in medulloblastoma in terms of prognosis and as a therapeutic target. Members of activated mTOR complex 1 (mTORC1) pathway, phospho-mTOR (p-mTOR) and phospho-S6 (p-S6) were examined by immunohistochemistry in formalin fixed paraffin embedded samples of 40 patients with medulloblastoma, and results were compared to clinical features and survival of patients. In proliferation assays, Daoy and UW228–2 medulloblastoma cell lines were tested by rapamycin, an mTORC1 inhibitor, and NVP-BEZ235, a dual mTOR and phosphatidylinositol 3-kinase (PI3K) inhibitor, each in monotherapy and in combination with cytostatic drugs (cisplatin, etoposide). Components of mTORC1 and mTORC2 complexes were also examined in these cell lines. Neither presence of p-mTOR (32.5 %) nor p-S6 (32.5 %) correlated with age, gender or histological subtype. In 22.5 % of cases simultaneous expression of p-mTOR and p-S6 was shown. Kaplan-Meier analysis showed inferior survival of patients expressing both marker proteins, but it was not statistically significant, probably due to low case number. UW228–2 cells had greater sensitivity to mTOR inhibitors, possibly due to its higher mTORC1 specific protein expression levels, compared to Daoy cells. In both cell lines antiproliferative effect of cytostatic drugs was significantly enhanced by mTOR inhibitors (p <0.05). Based on our in vitro and clinicopathological studies mTOR inhibitors may have a role in the future treatment of a subset of patients with medulloblastoma.

Original languageEnglish
JournalPathology and Oncology Research
Volume20
Issue number4
DOIs
Publication statusPublished - 2014

Fingerprint

Medulloblastoma
Sirolimus
S 6
Cytostatic Agents
Cell Line
Phosphatidylinositol 3-Kinase
Proteins
Survival
Kaplan-Meier Estimate
Etoposide
Paraffin
Formaldehyde
Cisplatin
Immunohistochemistry
Therapeutics

Keywords

  • Brain
  • Daoy
  • Medulloblastoma
  • mTOR inhibitors
  • mTORC1
  • Pediatric
  • Rapamycin
  • Survival
  • Tumor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pathology and Forensic Medicine

Cite this

mTOR Pathway As a Potential Target In a Subset of Human Medulloblastoma. / Pócza, Tímea; Sebestyén, A.; Turányi, Eszter; Krenács, T.; Márk, Ágnes; Sticz, Tamás Béla; Jakab, Zsuzsanna; Hauser, P.

In: Pathology and Oncology Research, Vol. 20, No. 4, 2014.

Research output: Contribution to journalArticle

Pócza, Tímea ; Sebestyén, A. ; Turányi, Eszter ; Krenács, T. ; Márk, Ágnes ; Sticz, Tamás Béla ; Jakab, Zsuzsanna ; Hauser, P. / mTOR Pathway As a Potential Target In a Subset of Human Medulloblastoma. In: Pathology and Oncology Research. 2014 ; Vol. 20, No. 4.
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AU - Márk, Ágnes

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