title: p53 apoptotic response to DNA damage dependent on bcl2 but not bax in head and neck squamous cell carcinoma lines.
abstract: BACKGROUND
  In many tumors, the p53 gene has been mutated or deleted. p53 null mutant mice are prone to development of a variety of neoplasms at an early age. In head and neck cancer, p53 mutations are detected in most cases. p53 has been shown to induce growth arrest, differentiation, and death when overexpressed in cancer cell lines. p53 responds to DNA damage by arresting the cell cycle in G1 or G2 phase until repair can be completed. If DNA damage is severe, p53 may trigger programmed cell death by means of proapoptotic genes such as bax. Studies have suggested that p53 target genes must be intact for proper functioning of the tumor suppressor.
  
  
  METHODS
  We stably expressed transcriptionally active p53 in head and neck squamous cell carcinoma (SCC) lines in which the endogenous gene was inactivated by mutation. We performed proliferation, cell death, cell cycle, and gene expression analysis in control clones and those treated with the DNA damaging agent etoposide.
  
  
  RESULTS
  These clones proliferated slowly with accumulation of cells at the G1/S phase boundary but did not undergo growth arrest or apoptosis. Coexpression of the proapoptotic gene bax (a known target of p53) failed to induce apoptosis in these clones. However, p53 expression sensitized these cells to DNA damage-induced apoptosis by means of inhibition of bcl2 protein levels.
  
  
  CONCLUSIONS
  We concluded that the p53 apoptotic response to DNA damage was dependent on bcl2 but not bax in head and neck SCC lines.
authors.affiliation: Center for Craniofacial Molecular Biology, Department of Otolaryngology-Head and Neck Surgery, Keck School of Medicine, 2250 Alcazar Street, CSA 103, Los Angeles, California 90033, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Crowe
authors.forename: Uttam K
authors.initials: UK
authors.lastname: Sinha
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002872:Chromosome Deletion; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D004249:DNA Damage / Q000502:physiology*; D054637:Dual-Specificity Phosphatases; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009154:Mutation; D017027:Protein Tyrosine Phosphatases; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; C084429:CDKN3 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases