title: Knocking down nucleolin expression in gliomas inhibits tumor growth and induces cell cycle arrest.
abstract: Nucleolin is a multifunctional protein whose expression often correlates with increased cellular proliferation. While the expression of nucleolin is often elevated in numerous cancers, its expression in normal human brain and in astrocytomas has not been previously reported. Using paraffin-embedded sections from normal adult autopsy specimens and glioma resection specimens, we demonstrate that nucleolin expression is limited in the normal human brain specifically to mature neurons, ependymal cells, and granular cells of the dentate gyrus. While astrocytes in the normal human brain do not express nucleolin at significant levels, glioblastoma cell lines and primary human astrocytoma cells exhibit considerable nucleolin expression. Reduction of nucleolin expression through siRNA-mediated knockdown in the U87MG glioblastoma cell line caused a dramatic decrease in cell proliferation and induced cell cycle arrest in vitro. Moreover, conditional siRNA knockdown of nucleolin expression in U87MG intracranial xenografts in nude mice caused dramatic reduction in tumor size. Taken together, these results implicate nucleolin in the regulation of human astrocytoma proliferation in vitro and tumorigenicity in vivo and suggest that nucleolin may represent a potential novel therapeutic target for astrocytomas.
authors.affiliation: Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Xu
authors.forename: Neel
authors.initials: N
authors.lastname: Joshi
authors.forename: Ashima
authors.initials: A
authors.lastname: Agarwal
authors.forename: Sonika
authors.initials: S
authors.lastname: Dahiya
authors.forename: Patrice
authors.initials: P
authors.lastname: Bittner
authors.forename: Erin
authors.initials: E
authors.lastname: Smith
authors.forename: Sara
authors.initials: S
authors.lastname: Taylor
authors.forename: David
authors.initials: D
authors.lastname: Piwnica-Worms
authors.forename: Jason
authors.initials: J
authors.lastname: Weber
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Leonard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001254:Astrocytoma / Q000503:physiopathology / Q000628:therapy*; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000503:physiopathology / Q000628:therapy*; D001973:Bromodeoxyuridine; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult; D000097796:Nucleolin; D000070584:Tripartite Motif Proteins
chemical_list: D001973:Bromodeoxyuridine; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D009687:Nuclear Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C064419:TRIM27 protein, human; D000070584:Tripartite Motif Proteins