title: The effect of Zhangfei/CREBZF on cell growth, differentiation, apoptosis, migration, and the unfolded protein response in several canine osteosarcoma cell lines.
abstract: BACKGROUND
  We had previously shown that the bLZip domain-containing transcription factor, Zhangfei/CREBZF inhibits the growth and the unfolded protein response (UPR) in cells of the D-17 canine osteosarcoma (OS) line and that the effects of Zhangfei are mediated by it stabilizing the tumour suppressor protein p53. To determine if our observations with D-17 cells applied more universally to canine OS, we examined three other independently isolated canine OS cell lines--Abrams, McKinley and Gracie.
  
  
  RESULTS
  Like D-17, the three cell lines expressed p53 proteins that were capable of activating promoters with p53 response elements on their own, and synergistically with Zhangfei. Furthermore, as with D-17 cells, Zhangfei suppressed the growth and UPR-related transcripts in the OS cell lines. Zhangfei also induced the activation of osteocalcin expression, a marker of osteoblast differentiation and triggered programmed cell death.
  
  
  CONCLUSIONS
  Osteosarcomas are common malignancies in large breeds of dogs. Although there has been dramatic progress in their treatment, these therapies often fail, leading to recurrence of the tumour and metastatic spread. Our results indicate that induction of the expression of Zhangfei in OS, where p53 is functional, may be an effective modality for the treatment of OS.
authors.affiliation: Department of Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada. rui.zhang@usask.ca.|Present address: Department of Basic Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, China. rui.zhang@usask.ca.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Flint Animal Cancer Center, Colorado State University, Fort Collins, CO, USA. doug.thamm@colostate.edu.
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Thamm
authors.affiliation: Department of Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK, Canada. vikram.misra@usask.ca.
authors.forename: Vikram
authors.initials: V
authors.lastname: Misra
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D050976:Basic-Leucine Zipper Transcription Factors / Q000502:physiology*; D001859:Bone Neoplasms / Q000503:physiopathology*; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D004283:Dog Diseases / Q000503:physiopathology*; D004285:Dogs; D012516:Osteosarcoma / Q000503:physiopathology*; D060888:Real-Time Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D056811:Unfolded Protein Response / Q000502:physiology*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D016159:Tumor Suppressor Protein p53