title: Disruptive TP53 mutation is associated with aggressive disease characteristics in an orthotopic murine model of oral tongue cancer.
abstract: OBJECTIVE
  To characterize tumor growth and metastatic potential in head and neck squamous cell carcinoma (HNSCC) cell lines in an orthotopic murine model of oral tongue cancer and to correlate TP53 mutation status with these findings.
  
  
  METHODS
  Cells from each of 48 HNSCC cell lines were orthotopically injected into the oral tongues of nude mice. Tumor volume, cervical lymph node metastasis, and mouse survival were recorded. Direct sequencing of the TP53 gene and Western blot analysis for the p53 protein after induction with 5-fluorouracil was conducted. Cell lines were categorized as either mutant TP53 or wild-type TP53, and lines with TP53 mutation were further categorized on the basis of type of mutation (disruptive or nondisruptive) and level of p53 protein expression. The behavior of tumors in these different groups was compared.
  
  
  RESULTS
  These 48 HNSCC cell lines showed a wide range of behavior from highly aggressive and metastatic to no tumor formation. Mice injected with cells harboring disruptive TP53 mutations had faster tumor growth, greater incidence of cervical lymph node metastasis, and shorter survival than mice injected with cells lacking these mutations.
  
  
  CONCLUSIONS
  HNSCC cell lines display a wide spectrum of behavior in an orthotopic model of oral cancer. Cell lines with disruptive TP53 mutations are more aggressive in this system, corroborating clinical reports that have linked these mutations to poor patient outcome.
authors: Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Daisuke
authors: D
authors: Sano
authors: Tong-Xin
authors: TX
authors: Xie
authors: Thomas J
authors: TJ
authors: Ow
authors: Mei
authors: M
authors: Zhao
authors: Curtis R
authors: CR
authors: Pickering
authors: Ge
authors: G
authors: Zhou
authors: Vlad C
authors: VC
authors: Sandulache
authors: David A
authors: DA
authors: Wheeler
authors: Richard A
authors: RA
authors: Gibbs
authors: Carlos
authors: C
authors: Caulin
authors: Jeffrey N
authors: JN
authors: Myers
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D016158:Genes, p53; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D000077195:Squamous Cell Carcinoma of Head and Neck; D014062:Tongue Neoplasms / Q000235:genetics* / Q000473:pathology*; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53