title: Activating transcription factor-2 in survival mechanisms in head and neck carcinoma cells.
abstract: BACKGROUND
  Activating transcription factor-2 (ATF2) is associated with tumor progression but is not well studied in head and neck squamous cell carcinoma (HNSCC). Its effects in stress and its importance in other survival mechanisms were studied.
  
  
  METHODS
  ATF2 expression and nuclear activation were confirmed in HNSCC. After modulation of ATF2, in vitro effects on proliferation and chemosensitivity were studied. Effects on in vivo tumor growth and interleukin 8 (IL-8) expression were determined. Tumor necrosis factor-alpha (TNF-α) treatment was used to further evaluate cytokine production and chemosensitivity.
  
  
  RESULTS
  Reductions of ATF2 resulted in significant nuclear p-ATF2 activation, cisplatin resistance, and augmented IL-8 expression without affecting in vivo tumor growth. In this setting, TNF increases p-p38 phosphorylation and chemosensitivity while further enhancing IL-8 production.
  
  
  CONCLUSIONS
  Our data suggest regulatory roles for ATF2 in TNF-related mechanisms of HNSCC. Its perturbation and nuclear activation are associated with significant effects on survival and cytokine production.
authors: Yale University School of Medicine Section of Otolaryngology, 333 Cedar St, Box 208041, New Haven, Connecticut 06520, USA. Dianne.duffey@yale.edu
authors: Dianne
authors: D
authors: Duffey
authors: Svetlana
authors: S
authors: Dolgilevich
authors: Sleiman
authors: S
authors: Razzouk
authors: Lina
authors: L
authors: Li
authors: Ross
authors: R
authors: Green
authors: Goutham Krishna
authors: GK
authors: Gorti
mesh_terms: D051698:Activating Transcription Factor 2 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D002453:Cell Cycle; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000378:metabolism*; D012680:Sensitivity and Specificity; D000077195:Squamous Cell Carcinoma of Head and Neck; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D051698:Activating Transcription Factor 2; D016207:Cytokines; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D002945:Cisplatin