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Insulin-like growth factor II is involved in the proliferation control of medulloblastoma and its cerebellar precursor cells

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Insulin-like growth factor II is involved in the proliferation control of medulloblastoma and its cerebellar precursor cells. / Hartmann, Wolfgang; Koch, Arend; Brune, Hendrik; Waha, Anke; Schüller, Ulrich; Dani, Indra; Denkhaus, Dorota; Langmann, Wilhelma; Bode, Udo; Wiestler, Otmar D; Schilling, Karl; Pietsch, Torsten.

In: AM J PATHOL, Vol. 166, No. 4, 04.2005, p. 1153-62.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Hartmann, W, Koch, A, Brune, H, Waha, A, Schüller, U, Dani, I, Denkhaus, D, Langmann, W, Bode, U, Wiestler, OD, Schilling, K & Pietsch, T 2005, 'Insulin-like growth factor II is involved in the proliferation control of medulloblastoma and its cerebellar precursor cells', AM J PATHOL, vol. 166, no. 4, pp. 1153-62. https://doi.org/10.1016/S0002-9440(10)62335-8

APA

Hartmann, W., Koch, A., Brune, H., Waha, A., Schüller, U., Dani, I., Denkhaus, D., Langmann, W., Bode, U., Wiestler, O. D., Schilling, K., & Pietsch, T. (2005). Insulin-like growth factor II is involved in the proliferation control of medulloblastoma and its cerebellar precursor cells. AM J PATHOL, 166(4), 1153-62. https://doi.org/10.1016/S0002-9440(10)62335-8

Vancouver

Hartmann W, Koch A, Brune H, Waha A, Schüller U, Dani I et al. Insulin-like growth factor II is involved in the proliferation control of medulloblastoma and its cerebellar precursor cells. AM J PATHOL. 2005 Apr;166(4):1153-62. https://doi.org/10.1016/S0002-9440(10)62335-8

Bibtex

@article{596f9c9b5e8e498baed48cd068e35271,
title = "Insulin-like growth factor II is involved in the proliferation control of medulloblastoma and its cerebellar precursor cells",
abstract = "Medulloblastomas (MBs), the most frequent malignant brain tumors of childhood, presumably originate from cerebellar neural precursor cells. An essential fetal mitogen involved in the pathogenesis of different embryonal tumors is insulin-like growth factor II (IGF-II). We screened human MB biopsies of the classic (CMB) and desmoplastic (DMB) variants for IGF2 transcripts of the four IGF2 promoters. We found IGF2 transcription from the imprinted promoter P3 to be significantly increased in the desmoplastic variant compared to the classic subgroup. This was not a result of loss of imprinting of IGF2 in desmoplastic tumors. We next examined the interaction of IGF-II and Sonic hedgehog (Shh), which serves as a critical mitogen for cerebellar granule cell precursors (GCPs) in the external granule cell layer from which DMBs are believed to originate. Mutations of genes encoding components of the Shh-Patched signaling pathway occur in approximately 50% of DMBs. To analyze the effects of IGF-II on Hedgehog signaling, we cultured murine GCP and human MB cells in the presence of Shh and Igf-II. In GCPs, a synergistic effect of Shh and Igf-II on proliferation and gli1 and cyclin D1 mRNA expression was found. Igf-II, but not Shh, induced phosphorylation of Akt and its downstream target Gsk-3beta. In six of nine human MB cell lines IGF-II displayed a growth-promoting effect that was mediated mainly through the IGF-I receptor. Together, our data point to an important role of IGF-II for the proliferation control of both cerebellar neural precursors and MB cells.",
keywords = "Animals, Blotting, Western, Brain, Cell Proliferation, Cells, Cultured, Cerebellar Neoplasms, DNA Primers, Fetus, Hedgehog Proteins, Humans, Medulloblastoma, Mice, Neurons, Promoter Regions, Genetic, RNA, Messenger, Receptor, Insulin, Reverse Transcriptase Polymerase Chain Reaction, Somatomedins, Stem Cells, Trans-Activators, Journal Article, Research Support, Non-U.S. Gov't",
author = "Wolfgang Hartmann and Arend Koch and Hendrik Brune and Anke Waha and Ulrich Sch{\"u}ller and Indra Dani and Dorota Denkhaus and Wilhelma Langmann and Udo Bode and Wiestler, {Otmar D} and Karl Schilling and Torsten Pietsch",
year = "2005",
month = apr,
doi = "10.1016/S0002-9440(10)62335-8",
language = "English",
volume = "166",
pages = "1153--62",
journal = "AM J PATHOL",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "4",

}

RIS

TY - JOUR

T1 - Insulin-like growth factor II is involved in the proliferation control of medulloblastoma and its cerebellar precursor cells

AU - Hartmann, Wolfgang

AU - Koch, Arend

AU - Brune, Hendrik

AU - Waha, Anke

AU - Schüller, Ulrich

AU - Dani, Indra

AU - Denkhaus, Dorota

AU - Langmann, Wilhelma

AU - Bode, Udo

AU - Wiestler, Otmar D

AU - Schilling, Karl

AU - Pietsch, Torsten

PY - 2005/4

Y1 - 2005/4

N2 - Medulloblastomas (MBs), the most frequent malignant brain tumors of childhood, presumably originate from cerebellar neural precursor cells. An essential fetal mitogen involved in the pathogenesis of different embryonal tumors is insulin-like growth factor II (IGF-II). We screened human MB biopsies of the classic (CMB) and desmoplastic (DMB) variants for IGF2 transcripts of the four IGF2 promoters. We found IGF2 transcription from the imprinted promoter P3 to be significantly increased in the desmoplastic variant compared to the classic subgroup. This was not a result of loss of imprinting of IGF2 in desmoplastic tumors. We next examined the interaction of IGF-II and Sonic hedgehog (Shh), which serves as a critical mitogen for cerebellar granule cell precursors (GCPs) in the external granule cell layer from which DMBs are believed to originate. Mutations of genes encoding components of the Shh-Patched signaling pathway occur in approximately 50% of DMBs. To analyze the effects of IGF-II on Hedgehog signaling, we cultured murine GCP and human MB cells in the presence of Shh and Igf-II. In GCPs, a synergistic effect of Shh and Igf-II on proliferation and gli1 and cyclin D1 mRNA expression was found. Igf-II, but not Shh, induced phosphorylation of Akt and its downstream target Gsk-3beta. In six of nine human MB cell lines IGF-II displayed a growth-promoting effect that was mediated mainly through the IGF-I receptor. Together, our data point to an important role of IGF-II for the proliferation control of both cerebellar neural precursors and MB cells.

AB - Medulloblastomas (MBs), the most frequent malignant brain tumors of childhood, presumably originate from cerebellar neural precursor cells. An essential fetal mitogen involved in the pathogenesis of different embryonal tumors is insulin-like growth factor II (IGF-II). We screened human MB biopsies of the classic (CMB) and desmoplastic (DMB) variants for IGF2 transcripts of the four IGF2 promoters. We found IGF2 transcription from the imprinted promoter P3 to be significantly increased in the desmoplastic variant compared to the classic subgroup. This was not a result of loss of imprinting of IGF2 in desmoplastic tumors. We next examined the interaction of IGF-II and Sonic hedgehog (Shh), which serves as a critical mitogen for cerebellar granule cell precursors (GCPs) in the external granule cell layer from which DMBs are believed to originate. Mutations of genes encoding components of the Shh-Patched signaling pathway occur in approximately 50% of DMBs. To analyze the effects of IGF-II on Hedgehog signaling, we cultured murine GCP and human MB cells in the presence of Shh and Igf-II. In GCPs, a synergistic effect of Shh and Igf-II on proliferation and gli1 and cyclin D1 mRNA expression was found. Igf-II, but not Shh, induced phosphorylation of Akt and its downstream target Gsk-3beta. In six of nine human MB cell lines IGF-II displayed a growth-promoting effect that was mediated mainly through the IGF-I receptor. Together, our data point to an important role of IGF-II for the proliferation control of both cerebellar neural precursors and MB cells.

KW - Animals

KW - Blotting, Western

KW - Brain

KW - Cell Proliferation

KW - Cells, Cultured

KW - Cerebellar Neoplasms

KW - DNA Primers

KW - Fetus

KW - Hedgehog Proteins

KW - Humans

KW - Medulloblastoma

KW - Mice

KW - Neurons

KW - Promoter Regions, Genetic

KW - RNA, Messenger

KW - Receptor, Insulin

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Somatomedins

KW - Stem Cells

KW - Trans-Activators

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/S0002-9440(10)62335-8

DO - 10.1016/S0002-9440(10)62335-8

M3 - SCORING: Journal article

C2 - 15793295

VL - 166

SP - 1153

EP - 1162

JO - AM J PATHOL

JF - AM J PATHOL

SN - 0002-9440

IS - 4

ER -