title: Disrupting the interaction between HOX and PBX causes necrotic and apoptotic cell death in the renal cancer lines CaKi-2 and 769-P.
abstract: OBJECTIVE
  The HOX genes are a family of homeodomain containing transcription factors that determine embryonic tissue identity and also have regulatory and oncogenic roles in adult cells. We quantified the expression of HOX genes in normal kidney tissue, primary tumors and derived cell lines, and examined their role in renal cancer cell survival.
  
  
  METHODS
  Quantitative polymerase chain reaction was used to evaluate HOX gene expression in cells and tissues. HOX gene function was disrupted using a peptide that blocks the interaction between HOX proteins and their PBX cofactor. Apoptosis was assessed by annexin/propidium iodide staining and direct measurement of caspase activity.
  
  
  RESULTS
  Primary renal tumors and derived cell lines showed abnormal HOX gene expression. Furthermore, blocking HOX activity by targeting the interaction between HOX and its cofactor PBX caused apoptotic and necrotic cell death in the renal cancer cell lines CaKi-2 and 769-P, while sparing normal adult kidney cells.
  
  
  CONCLUSIONS
  Our findings suggest that the HOX/PBX dimer is a potential therapeutic target in renal cancer.
authors.affiliation: Postgraduate Medical School, University of Surrey, Guildford and Head and Neck Unit, London, United Kingdom.
authors.forename: Liesl
authors.initials: L
authors.lastname: Shears
authors.forename: Lynn
authors.initials: L
authors.lastname: Plowright
authors.forename: Kevin
authors.initials: K
authors.lastname: Harrington
authors.forename: Hardev S
authors.initials: HS
authors.lastname: Pandha
authors.forename: Richard
authors.initials: R
authors.lastname: Morgan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D005801:Genes, Homeobox / Q000502:physiology*; D007680:Kidney Neoplasms / Q000235:genetics; D051379:Mice; D009336:Necrosis / Q000473:pathology; D012334:RNA, Neoplasm / Q000032:analysis; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D012334:RNA, Neoplasm; D014157:Transcription Factors