title: CDK2 knockdown enhances head and neck cancer cell radiosensitivity.
abstract: OBJECTIVE
  Cyclin-dependent kinase 2 (CDK2) is critically involved in cell cycling and has been proposed as a potential cancer target. It remains largely elusive whether CDK2 targeting alters the tumor cell radiosensitivity.
  
  
  METHODS
  CDK2(-/-) and wild type (WT) mouse embryonic fibroblasts (MEF) as well as six human head and neck squamous cell carcinoma (HNSCC) cell lines (SAS, FaDu, Cal-33, HSC-4, UTSCC-5, UTSCC-8) were used. Upon CDK2 knockdown using small interfering technology, colony formation, DNA double-strand breaks (DSB), cell cycle distribution and expression and phosphorylation of major proteins regulating cell cycle and DNA damage repair were examined.
  
  
  RESULTS
  CDK2(-/-) MEF and CDK2 HNSCC knockdown cell cultures were more radiosensitive than the corresponding controls. Repair of DSB was attenuated under CDK2 knockout or knockdown. In contrast to data in MEF, combined CDK2 knockdown with irradiation showed no cell cycling alterations in SAS and FaDu cultures. Importantly, CDK2 knockdown failed to radiosensitize SAS and FaDu when cultured in a more physiological three-dimensional (3D) extracellular matrix environment.
  
  
  CONCLUSIONS
  Our findings suggest that targeting of CDK2 radiosensitizes HNSCC cells growing as monolayer. Additional studies performed under more physiological conditions are warranted to clarify the potential of CDK2 as target in radiotherapy.
authors: OncoRay - National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, 01307 Dresden, Germany.
authors: Ahmed
authors: A
authors: Soffar
authors: Katja
authors: K
authors: Storch
authors: Eiman
authors: E
authors: Aleem
authors: Nils
authors: N
authors: Cordes
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D045744:Cell Line, Tumor; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D055785:Gene Knockdown Techniques; D006258:Head and Neck Neoplasms / Q000473:pathology* / Q000503:physiopathology* / Q000532:radiotherapy; D006801:Humans; D051379:Mice; D011829:Radiation Dosage; D011836:Radiation Tolerance
chemical_list: C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2