title: NUMB does not impair growth and differentiation status of experimental gliomas.
abstract: The cell fate determinant NUMB orchestrates asymmetric cell division in flies and mammals and has lately been suggested to have a tumor suppressor function in breast and lung cancer. Here, we studied NUMB in the context of malignant gliomas. We used ectopic expression of NUMB in order to inhibit proliferation and induce differentiation in glioma cells by alteration of Notch, Hedgehog and p53 signaling. We found that NUMB is consistently expressed in glioma biopsies with predominance of NUMB2/4 isoforms as determined by isoform-specific real-time PCR and Western blotting. Upon lentiviral overexpression, in vitro proliferation rate and the grade of differentiation as assessed by morphology and expression of neural and glial markers remained unchanged. Orthotopic xenografts of NUMB-transduced human U87 glioma cells could be established in nude rats without impairing engraftment or causing significant changes in morphology based on magnetic resonance imaging (MRI). The previously reported alteration of Hedgehog and p53 signaling by NUMB could not be recapitulated in glioma cells. We thus show that in experimental gliomas, NUMB overexpression most likely does not exert a tumor suppressor function such as seen in epithelial cancers.
authors.affiliation: Department of Biomedicine, University of Bergen, Norway. philipp.euskirchen@charite.de
authors.forename: Philipp
authors.initials: P
authors.lastname: Euskirchen
authors.forename: Kai-Ove
authors.initials: KO
authors.lastname: Skaftnesmo
authors.forename: Peter C
authors.initials: PC
authors.lastname: Huszthy
authors.forename: Narve
authors.initials: N
authors.lastname: Brekkå
authors.forename: Rolf
authors.initials: R
authors.lastname: Bjerkvig
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Jacobs
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Miletic
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D051381:Rats; D011923:Rats, Nude; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C113026:NUMB protein, human; D020033:Protein Isoforms; D051880:Receptors, Notch; D016159:Tumor Suppressor Protein p53