Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells
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Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells. / Yang, Zeng-Jie; Ellis, Tammy; Markant, Shirley L; Read, Tracy-Ann; Kessler, Jessica D; Bourboulas, Melissa; Schüller, Ulrich; Machold, Robert; Fishell, Gord; Rowitch, David H; Wainwright, Brandon J; Wechsler-Reya, Robert J.
In: CANCER CELL, Vol. 14, No. 2, 12.08.2008, p. 135-45.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells
AU - Yang, Zeng-Jie
AU - Ellis, Tammy
AU - Markant, Shirley L
AU - Read, Tracy-Ann
AU - Kessler, Jessica D
AU - Bourboulas, Melissa
AU - Schüller, Ulrich
AU - Machold, Robert
AU - Fishell, Gord
AU - Rowitch, David H
AU - Wainwright, Brandon J
AU - Wechsler-Reya, Robert J
PY - 2008/8/12
Y1 - 2008/8/12
N2 - Medulloblastoma is the most common malignant brain tumor in children, but the cells from which it arises remain unclear. Here we examine the origin of medulloblastoma resulting from mutations in the Sonic hedgehog (Shh) pathway. We show that activation of Shh signaling in neuronal progenitors causes medulloblastoma by 3 months of age. Shh pathway activation in stem cells promotes stem cell proliferation but only causes tumors after commitment to-and expansion of-the neuronal lineage. Notably, tumors initiated in stem cells develop more rapidly than those initiated in progenitors, with all animals succumbing by 3-4 weeks. These studies suggest that medulloblastoma can be initiated in progenitors or stem cells but that Shh-induced tumorigenesis is associated with neuronal lineage commitment.
AB - Medulloblastoma is the most common malignant brain tumor in children, but the cells from which it arises remain unclear. Here we examine the origin of medulloblastoma resulting from mutations in the Sonic hedgehog (Shh) pathway. We show that activation of Shh signaling in neuronal progenitors causes medulloblastoma by 3 months of age. Shh pathway activation in stem cells promotes stem cell proliferation but only causes tumors after commitment to-and expansion of-the neuronal lineage. Notably, tumors initiated in stem cells develop more rapidly than those initiated in progenitors, with all animals succumbing by 3-4 weeks. These studies suggest that medulloblastoma can be initiated in progenitors or stem cells but that Shh-induced tumorigenesis is associated with neuronal lineage commitment.
KW - Animals
KW - Basic Helix-Loop-Helix Transcription Factors
KW - Cell Differentiation
KW - Cell Lineage
KW - Cell Proliferation
KW - Gene Deletion
KW - Glial Fibrillary Acidic Protein
KW - Hedgehog Proteins
KW - Humans
KW - Hyperplasia
KW - Integrases
KW - Medulloblastoma
KW - Mice
KW - Mice, Knockout
KW - Neurons
KW - Patched Receptors
KW - Phenotype
KW - Precancerous Conditions
KW - Receptors, Cell Surface
KW - Stem Cells
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.ccr.2008.07.003
DO - 10.1016/j.ccr.2008.07.003
M3 - SCORING: Journal article
C2 - 18691548
VL - 14
SP - 135
EP - 145
JO - CANCER CELL
JF - CANCER CELL
SN - 1535-6108
IS - 2
ER -