title: Inhibitor of differentiation 4 drives brain tumor-initiating cell genesis through cyclin E and notch signaling.
abstract: Cellular origins and genetic factors governing the genesis and maintenance of glioblastomas (GBM) are not well understood. Here, we report a pathogenetic role of the developmental regulator Id4 (inhibitor of differentiation 4) in GBM. In primary murine Ink4a/Arf(-/-) astrocytes, and human glioma cells, we provide evidence that enforced Id4 can drive malignant transformation by stimulating increased cyclin E to produce a hyperproliferative profile and by increased Jagged1 expression with Notch1 activation to drive astrocytes into a neural stem-like cell state. Thus, Id4 plays an integral role in the transformation of astrocytes via its combined actions on two-key cell cycle and differentiation regulatory molecules.
authors.affiliation: School of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
authors.forename: Hye-Min
authors.initials: HM
authors.lastname: Jeon
authors.forename: Xun
authors.initials: X
authors.lastname: Jin
authors.forename: Joong-Seob
authors.initials: JS
authors.lastname: Lee
authors.forename: Se-Yeong
authors.initials: SY
authors.lastname: Oh
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Sohn
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Park
authors.forename: Kyeung Min
authors.initials: KM
authors.lastname: Joo
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
authors.forename: Ronald A
authors.initials: RA
authors.lastname: DePinho
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
authors.forename: Hyunggee
authors.initials: H
authors.lastname: Kim
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D019927:Cyclin E / Q000378:metabolism*; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D051796:Inhibitor of Differentiation Proteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: D002135:Calcium-Binding Proteins; D019927:Cyclin E; C490128:ID4 protein, human; D051796:Inhibitor of Differentiation Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; D012333:RNA, Messenger; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins