title: Protein alterations associated with temozolomide resistance in subclones of human glioblastoma cell lines.
abstract: Temozolomide (TMZ) is the standard chemotherapeutic agent for human malignant glioma, but intrinsic or acquired chemoresistance represents a major obstacle to successful treatment of this highly lethal group of tumours. Obtaining better understanding of the molecular mechanisms underlying TMZ resistance in malignant glioma is important for the development of better treatment strategies. We have successfully established a passage control line (D54-C10) and resistant variants (D54-P5 and D54-P10) from the parental TMZ-sensitive malignant glioma cell line D54-C0. The resistant sub-cell lines showed alterations in cell morphology, enhanced cell adhesion, increased migration capacities, and cell cycle arrests. Proteomic analysis identified a set of proteins that showed gradual changes in expression according to their 50% inhibitory concentration (IC(50)). Successful validation was provided by transcript profiling in another malignant glioma cell line U87-MG and its resistant counterparts. Moreover, three of the identified proteins (vimentin, cathepsin D and prolyl 4-hydroxylase, beta polypeptide) were confirmed to be upregulated in high-grade glioma. Our data suggest that acquired TMZ resistance in human malignant glioma is associated with promotion of malignant phenotypes, and our reported molecular candidates may serve not only as markers of chemoresistance but also as potential therapeutic targets in the treatment of TMZ-resistant human malignant glioma, providing a platform for future investigations.
authors: Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, 21 Sassoon Road, Pokfulam, Hong Kong, People's Republic of China.
authors: Stella
authors: S
authors: Sun
authors: T S
authors: TS
authors: Wong
authors: X Q
authors: XQ
authors: Zhang
authors: Jenny K S
authors: JK
authors: Pu
authors: Nikki P
authors: NP
authors: Lee
authors: Philip J R
authors: PJ
authors: Day
authors: Gloria K B
authors: GK
authors: Ng
authors: W M
authors: WM
authors: Lui
authors: Gilberto K K
authors: GK
authors: Leung
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002448:Cell Adhesion; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D015180:Electrophoresis, Gel, Two-Dimensional; D005434:Flow Cytometry; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000077204:Temozolomide; D014945:Wound Healing
chemical_list: D018906:Antineoplastic Agents, Alkylating; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D003606:Dacarbazine; D000077204:Temozolomide