Abstract
Sonic hedgehog (Hh) developmental pathway deregulation has been proven to play an essential role in several malignancies as neuroblastoma. We found that Hh signaling is active in neuroblastoma, as most pathway components, including GLI1, were expressed in cell lines and tumor samples. Furthermore, SHH ligand expression was found in cell lines and tumors, and GLI1 up-regulation was achieved in response to SHH treatment, suggesting an autocrine mechanism of aberrant activation. A decrease of proliferation and tumorigenic potential, as well as increased apoptosis and a dramatic decrease in the percentage of CD15+ cell population were produced upon Hh inhibition by cyclopamine.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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AC133 Antigen
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Antigens, CD / biosynthesis
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Apoptosis / drug effects
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Biomarkers, Tumor / biosynthesis
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Cell Growth Processes / drug effects
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Cell Line, Tumor
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Female
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Fucosyltransferases / biosynthesis
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Gene Expression Regulation, Neoplastic / drug effects
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Glycoproteins / biosynthesis
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Hedgehog Proteins / antagonists & inhibitors*
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Hedgehog Proteins / genetics
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Hedgehog Proteins / metabolism
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Humans
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Lewis X Antigen / biosynthesis
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Male
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Neoplastic Stem Cells / metabolism
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Neoplastic Stem Cells / pathology
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Neuroblastoma / drug therapy
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Neuroblastoma / genetics
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Neuroblastoma / metabolism*
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Neuroblastoma / pathology
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Peptides
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Signal Transduction / drug effects
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Transcription Factors / antagonists & inhibitors
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Transcription Factors / biosynthesis
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Transcription Factors / genetics
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Veratrum Alkaloids / pharmacology*
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Zinc Finger Protein GLI1
Substances
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AC133 Antigen
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Antigens, CD
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Biomarkers, Tumor
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GLI1 protein, human
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Glycoproteins
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Hedgehog Proteins
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Lewis X Antigen
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PROM1 protein, human
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Peptides
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SHH protein, human
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Transcription Factors
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Veratrum Alkaloids
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Zinc Finger Protein GLI1
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FUT4 protein, human
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Fucosyltransferases
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cyclopamine