title: Expression profile of frizzled receptors in human medulloblastomas.
abstract: Secreted WNT proteins signal through ten receptors of the frizzled (FZD) family. Because of the relevance of the WNT/β-catenin (CTNNB1) signaling pathway in medulloblastomas (MBs), we investigated the expression of all ten members of the FZD gene family (FZD1-10) in 17 human MBs, four MB cell lines and in normal human cerebellum, using real-time PCR. We found that FZD2 transcript was over-expressed in all MBs and MB cell lines. Western blot analysis confirmed the expression of FZD2 at the protein level. Moreover, the levels of FZD2 transcript were found to correlate with those of ASPM transcript, a marker of mitosis essential for mitotic spindle function. Accordingly, ASPM mRNA was expressed at a very low level in the adult, post-mitotic, human cerebellum, at higher levels in fetal cerebellum and at highest levels in MB tissues and cell lines. Unlike FZD2, the other FZDs were overexpressed (e.g., FZD1, FZD3 and FZD8) or underexpressed (e.g., FZD7, FZD9 and FZD10) in a case-restricted manner. Interestingly, we did not find any nuclear immuno-reactivity to CTNNB1 in four MBs over-expressing both FZD2 and other FZD receptors, confirming the lack of nuclear CTNNB1 staining in the presence of increased FZD expression, as in other tumor types. Overall, our results indicate that altered expression of FZD2 might be associated with a proliferative status, thus playing a role in the biology of human MBs, and possibly of cerebellar progenitors from which these malignancies arise.
authors.affiliation: UO Neuro-oncologia Molecolare-Neurologia VIII, Fondazione IRCCS, Istituto Neurologico "C. Besta", Via Celoria 11, 20133 Milan, Italy. ettore.salsano@istituto-besta.it
authors.forename: Ettore
authors.initials: E
authors.lastname: Salsano
authors.forename: Rosina
authors.initials: R
authors.lastname: Paterra
authors.forename: Miriam
authors.initials: M
authors.lastname: Figus
authors.forename: Francesca
authors.initials: F
authors.lastname: Menghi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Maderna
authors.forename: Bianca
authors.initials: B
authors.lastname: Pollo
authors.forename: Carlo Lazzaro
authors.initials: CL
authors.lastname: Solero
authors.forename: Luca
authors.initials: L
authors.lastname: Massimi
authors.forename: Gaetano
authors.initials: G
authors.lastname: Finocchiaro
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002648:Child; D016000:Cluster Analysis; D051157:Frizzled Receptors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
chemical_list: C467202:ASPM protein, human; D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D051157:Frizzled Receptors; D009419:Nerve Tissue Proteins; D051176:beta Catenin