title: The interaction between C35 and ΔNp73 promotes chemo-resistance in ovarian cancer cells.
abstract: BACKGROUND
  The purpose of this study was to characterise the oncogenic roles of C35, a novel protein binding partner of ΔNp73, in ovarian cancer and to investigate the functional significance of C35-ΔNp73 interaction in the regulation of chemo-resistance.
  
  
  METHODS
  C35 expression was evaluated by quantitative real-time PCR in human ovarian cancer tissues and cell lines. The aggressiveness of ovarian cancer cells overexpressing C35 was examined by cell proliferation, migration, soft agar and nude mouse xenograft. The significance of C35-ΔNp73 interaction in chemo-resistance was evaluated by apoptosis assays and cell viability after cisplatin treatment.
  
  
  RESULTS
  The expression of C35 was significantly enhanced in human ovarian cancer tissues. Overexpression of C35 augmented proliferation, migration and tumourigenicity in ovarian cancer cell lines. C35 knockdown inhibited cell motility and cell growth. The co-expression of C35 and ΔNp73 by transient or stable transfection in ovarian cancer cells induced greater resistance to cisplatin treatment than did transfection with C35 or ΔNp73 alone. The cisplatin resistance was demonstrated to be caused by increased AKT and NFκB activity induced by C35-ΔNp73.
  
  
  CONCLUSIONS
  Our results suggest that ΔNp73 might cooperate with C35 to promote tumour progression and contribute to cisplatin resistance in ovarian cancer cells. Future studies of the functional roles of ΔNp73 and C35 will provide insight that will aid in the establishment of new strategies and more effective therapies.
authors.affiliation: Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region.
authors.forename: T H-Y
authors.initials: TH
authors.lastname: Leung
authors.forename: S C-S
authors.initials: SC
authors.lastname: Wong
authors.forename: K K-L
authors.initials: KK
authors.lastname: Chan
authors.forename: D W
authors.initials: DW
authors.lastname: Chan
authors.forename: A N-Y
authors.initials: AN
authors.lastname: Cheung
authors.forename: H Y-S
authors.initials: HY
authors.lastname: Ngan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents; D045744:Cell Line, Tumor; D002945:Cisplatin; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism* / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism* / Q000502:physiology; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000378:metabolism* / Q000502:physiology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C517054:MIEN1 protein, human; D016328:NF-kappa B; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human; D051057:Proto-Oncogene Proteins c-akt; D002945:Cisplatin