2011PubMedRequires access

Favourable prognosis in medulloblastoma with extensive nodularity is associated with mitogen-activated protein kinase upregulation.

Jarosław Jóźwiak, Iwona Sontowska, Barbara Bikowska, Wiesława Grajkowska, Ryszard Galus, Marcin Roszkowski

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Abstract

Medulloblastoma with extensive nodularity (MBEN) is the only type of medulloblastoma (MB), an aggressive CNS tumour of childhood, that is connected with favourable prognosis. In patients with MBEN tumour resection and chemotherapy are sometimes sufficient. While development of other types of MB is usually connected with activation of the wingless pathway, sonic hedgehog pathway or mammalian target of rapamycin (mTor) pathway, little is known about the molecular basis of MBEN pathophysiology. In the present paper we evaluated activation of the mTor pathway and kinases upstream of mTor, mitogen-activated protein kinase (MAPK/Erk) and protein kinase B (PKB/Akt) in an MBEN sample. Using western blot technique with antibodies directed against active, phosphorylated forms of proteins, we found upregulation of mTor, Akt and Erk. Thus we postulate that the mTor pathway, often implicated in the development of CNS tumours, is also responsible for MBEN progression. Especially interesting seems implication of Erk and other kinases belonging to the same pathway: mitogen-activated protein kinase kinase (MEK-1) or phospho-ribosomal S6 kinase-1 (p90 RSK1), whose activity we usually demonstrate in more benign neoplasms. However, it remains to be clarified whether Erk pathway activation is actually prognostic for benign tumour development.

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What this paper is about

Medulloblastoma with extensive nodularity (MBEN) is the only type of medulloblastoma (MB), an aggressive CNS tumour of childhood, that is connected with favourable prognosis. In patients with MBEN tumour resection and chemotherapy are sometimes sufficient. While development of other types of MB is usually connected with activation of the wingless pathway, sonic hedgehog pathway or mammalian target of rapamycin (mTor) pathway, little is known about the molecular basis of MBEN pathophysiology. In the present paper we evaluated activation of the mTor pathway and kinases upstream of mTor, mitogen-activated protein kinase (MAPK/Erk) and protein kinase B (PKB/Akt) in an MBEN sample. Using western blot technique with antibodies directed against active, phosphorylated forms of proteins, we found upregulation of mTor, Akt and Erk. Thus we postulate that the mTor pathway, often implicated in the development of CNS tumours, is also responsible for MBEN progression. Especially interesting seems implication of Erk and other kinases belonging to the same pathway: mitogen-activated protein kinase kinase (MEK-1) or phospho-ribosomal S6 kinase-1 (p90 RSK1), whose activity we usually demonstrate in more benign neoplasms. However, it remains to be clarified whether Erk pathway activation is actually prognostic for benign tumour development.

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Available abstract

Medulloblastoma with extensive nodularity (MBEN) is the only type of medulloblastoma (MB), an aggressive CNS tumour of childhood, that is connected with favourable prognosis. In patients with MBEN tumour resection and chemotherapy are sometimes sufficient. While development of other types of MB is usually connected with activation of the wingless pathway, sonic hedgehog pathway or mammalian target of rapamycin (mTor) pathway, little is known about the molecular basis of MBEN pathophysiology. In the present paper we evaluated activation of the mTor pathway and kinases upstream of mTor, mitogen-activated protein kinase (MAPK/Erk) and protein kinase B (PKB/Akt) in an MBEN sample. Using western blot technique with antibodies directed against active, phosphorylated forms of proteins, we found upregulation of mTor, Akt and Erk. Thus we postulate that the mTor pathway, often implicated in the development of CNS tumours, is also responsible for MBEN progression. Especially interesting seems implication of Erk and other kinases belonging to the same pathway: mitogen-activated protein kinase kinase (MEK-1) or phospho-ribosomal S6 kinase-1 (p90 RSK1), whose activity we usually demonstrate in more benign neoplasms. However, it remains to be clarified whether Erk pathway activation is actually prognostic for benign tumour development.

Key concepts: MAPK/ERK pathway, PI3K/AKT/mTOR pathway, Protein kinase B, Ribosomal s6 kinase, Kinase, Cancer research, c-Raf, Protein kinase A

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Favourable prognosis in medulloblastoma with extensive nodularity is associated with mitogen-activated protein kinase upregulation. — Research Paper | ScholarLens