title: Doublecortin is preferentially expressed in invasive human brain tumors.
abstract: Doublecortin (DCX) is required for neuroblastic migration during the development of the cerebral cortex. DCX is a microtubule-associated protein that plays a role in cellular motility. These facts led us to hypothesize that DCX is increased in invasive brain tumors. DCX expression was assessed in 69 paraffin-embedded brain tumors of neuroepithelial origin. In addition, mouse brain sections of the subventricular zone and dentate gyrus were used as positive controls for immunostaining, and specificity of antibody staining was demonstrated by peptide neutralization. DCX was highly expressed in both high-grade invasive tumors (glioblastoma, n=11; anaplastic astrocytoma/oligoastrocytoma, n=7; and medulloblastoma/PNET, n=6) and low-grade invasive tumors (oligodendroglioma, n=3; and astrocytoma/oligoastrocytoma, n=5). However, DCX was less intensely expressed in the circumscribed group of tumors (pilocytic astrocytoma, n=6; ependymoma/subependymoma, n=7; dysembryoplastic neuroepithelial tumor, n=4; ganglioglioma, n=2; meningioma, n=9; and schwannoma, n=9). By the Cochran-Mantel-Haenszel statistical test, the circumscribed group was significantly different from both the high-grade invasive group (P<0.0001) and the low-grade invasive group (P<0.0001). We conclude that DCX is preferentially expressed in invasive brain tumors. In addition, DCX immunostaining was stronger at the margin of the tumor than at the center. For a subset of these tumors, we also detected DCX mRNA and protein by Northern and Western blotting. DCX mRNA and protein was detected in glioma cell lines by Northern blotting, immunofluorescence microscopy and Western blotting. Collectively, the immunohistochemistry, Western blots and Northern blots conclusively demonstrate expression of DCX by human brain tumors.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Daou
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Smith
authors.forename: N Scott
authors.initials: NS
authors.lastname: Litofsky
authors.forename: Chung C
authors.initials: CC
authors.lastname: Hsieh
authors.forename: Alonzo H
authors.initials: AH
authors.lastname: Ross
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D018891:Dentate Gyrus / Q000737:chemistry; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005910:Glioma / Q000737:chemistry* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000032:analysis* / Q000235:genetics; D008870:Microtubules / Q000737:chemistry / Q000502:physiology; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D009479:Neuropeptides / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics
chemical_list: C000714328:DCX protein, human; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D012333:RNA, Messenger