title: Gene expression profiling of the hedgehog signaling pathway in human meningiomas.
abstract: The Hedgehog (Hh) signaling pathway has an important role during embryogenesis and in adult life, regulating proliferation, angiogenesis, matrix remodeling and stem-cell renewal. Deregulation of the Hh pathway is involved in tumor development, since mutations in several components of this pathway were found in patients with basal cell carcinoma, medulloblastoma and other tumors; however, the role of Hh in meningiomas has not been studied yet. Meningiomas represent 30% of primary cranial tumors, are mostly benign and prevail in the second half of life. Novel therapies for meningiomas such as targeted molecular agents could use Hh pathway components. To provide information concerning molecular alterations, by use of real-time RT-PCR, we studied expression at the mRNA level of 32 Hh pathway and target genes in 36 meningioma specimens of different grades. mRNA levels of 16 genes, involved mainly in Hh pathway activation and cell proliferation, increased in meningiomas in comparison with normal tissue, whereas those of 7 genes, mainly related to Hh pathway repression, decreased. The most significant changes occurred in signal transduction (SMO) and GLI-transcription factor genes, and the target FOXM1 mRNA attained the highest values; their over-expression was found in aggressive and in benign tumors. Some proliferation-related genes (SPP1, IGF2) were overexpressed in higher meningioma grades. A correlation in expression between genes with a similar function was also found. Our results show a marked activation of the Hh pathway in meningiomas, which may be important for their biological and clinical characterization and would be useful for gene therapy.
authors.affiliation: UMR745, INSERM, Université Paris-Descartes, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Laurendeau
authors.forename: Marcela
authors.initials: M
authors.lastname: Ferrer
authors.forename: Delia
authors.initials: D
authors.lastname: Garrido
authors.forename: Nicky
authors.initials: N
authors.lastname: D'Haene
authors.forename: Patricia
authors.initials: P
authors.lastname: Ciavarelli
authors.forename: Armando
authors.initials: A
authors.lastname: Basso
authors.forename: Michel
authors.initials: M
authors.lastname: Vidaud
authors.forename: Ivan
authors.initials: I
authors.lastname: Bieche
authors.forename: Isabelle
authors.initials: I
authors.lastname: Salmon
authors.forename: Irene
authors.initials: I
authors.lastname: Szijan
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008297:Male; D008579:Meningioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D018709:Statistics, Nonparametric
chemical_list: D014408:Biomarkers, Tumor; D053823:Hedgehog Proteins; D012333:RNA, Messenger
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