Disruptive TP53 mutation is associated with aggressive disease characteristics in an orthotopic murine model of oral tongue cancer.

TitleDisruptive TP53 mutation is associated with aggressive disease characteristics in an orthotopic murine model of oral tongue cancer.
Publication TypeJournal Article
Year of Publication2011
AuthorsSano, D, Xie, T-X, Ow, TJ, Zhao, M, Pickering, CR, Zhou, G, Sandulache, VC, Wheeler, DA, Gibbs, RA, Caulin, C, Myers, JN
JournalClin Cancer Res
Volume17
Issue21
Pagination6658-70
Date Published2011 Nov 01
ISSN1078-0432
KeywordsAnimals, Carcinoma, Squamous Cell, Cell Line, Tumor, Disease Models, Animal, Genes, p53, Head and Neck Neoplasms, Humans, Male, Mice, Mice, Nude, Mutation, Squamous Cell Carcinoma of Head and Neck, Tongue Neoplasms, Transplantation, Heterologous, Tumor Suppressor Protein p53
Abstract

PURPOSE: 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.EXPERIMENTAL DESIGN: 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.

DOI10.1158/1078-0432.CCR-11-0046
Alternate JournalClin. Cancer Res.
PubMed ID21903770
PubMed Central IDPMC3207013
Grant ListR01 DE014613-08 / DE / NIDCR NIH HHS / United States
P30 CA016672-35 / CA / NCI NIH HHS / United States
P30 CA016672 / CA / NCI NIH HHS / United States
P50 CA097007 / CA / NCI NIH HHS / United States
CA016672 / CA / NCI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
T32 CA060374 / CA / NCI NIH HHS / United States
P50 CA097007-09 / CA / NCI NIH HHS / United States
R01 DE014613 / DE / NIDCR NIH HHS / United States
R01 DE14613 / DE / NIDCR NIH HHS / United States
T32 CA060374-15 / CA / NCI NIH HHS / United States
T32CA60374 / CA / NCI NIH HHS / United States
P50CA097007 / CA / NCI NIH HHS / United States