title: BCL-2 family proteins modulate radiosensitivity in human malignant glioma cells.
abstract: Radiotherapy is the standard treatment for glioblastoma. Here, we assessed the radiosensitivity of 12 human malignant glioma cell lines in vitro and correlated these data with irradiation-induced cell cycle changes, chemosensitivity profiles and BCL-2 family protein expression. Irradiation at 3 Gy failed to cause major cell cycle perturbations. Radioresistance was associated with collateral sensitivity to the topoisomerase II inhibitors, teniposide and doxorubicin. High levels of BCL-XL and low levels of BAX were independently linked to radioresistance. Ectopic expression of a BAX transgene induced radiosensitization in the LN-18 cell line. Thus, BCL-2 family protein expression modulates radiosensitivity in human glioma cells and targeted alterations in BCL-2 family protein expression are a promising strategy to improve the therapeutic efficacy of radiotherapy for gliomas.
authors.affiliation: Department of Neurology, University of Tübingen, Germany.
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Streffer
authors.forename: Andreas
authors.initials: A
authors.lastname: Rimner
authors.forename: Johannes
authors.initials: J
authors.lastname: Rieger
authors.forename: Ulrike
authors.initials: U
authors.lastname: Naumann
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Rodemann
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001932:Brain Neoplasms; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D018014:Gene Transfer Techniques; D005910:Glioma; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis* / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology / Q000528:radiation effects; D051028:bcl-2-Associated X Protein
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein