title: Expression of phosphorylated Akt in oral carcinogenesis and its induction by nicotine and alkaline stimulation.
abstract: BACKGROUND
  In Taiwan, it is well documented that cigarette smoking and areca nut chewing contribute to the risk of oral squamous cell carcinoma (OSCC). The role of phosphorylated Akt (p-Akt) in oral carcinogenesis induced by nicotine and alkaline environments was investigated.
  
  
  METHODS
  Immunohistochemistry (IHC) was used to detect p-Akt expression in cancerous (n = 30) precancerous (n = 30), and normal mucosa tissues (n = 10). Western blotting was used to detect time-dependent induction of p-Akt by 100 microM nicotine in normal human bronchial epithelial cell (NHBE), normal human oral keratinocytes (NHOK), immortalized human epithelial cells (HaCaT) and OEC-M1 cells, dose-dependent induction of p-Akt in OEC-M1 and HaCaT cells and pH effect of p-Akt in OEC-M1. The unpaired t-test and the Fisher's exact test were used to analyze the p-Akt immunoreactivity in various groups and its association with clinicopathological parameters.
  
  
  RESULTS
  Higher p-Akt expression in cancerous group than in normal mucosa (P = 0.0002) and precancerous (P = 0.0049) groups was observed. A time-dependent increase in p-Akt in the NHBE, NHOK, HaCaT and OEC-M1 cell lines was observed with 100 microM nicotine treatment. The dose-dependent increase in p-Akt by nicotine treatment in HaCaT and OEC-M1 cells was obviously observed. Higher p-Akt expression in more alkaline environment (pH 8.0) was observed than at pH 7.4 in OEC-M1 cells.
  
  
  CONCLUSIONS
  A potential role for increased p-Akt may relate to the dose and time of nicotine use. The potential role of an alkaline environment to enhance nicotine-related oral carcinogenesis may exist.
authors.affiliation: Oral & Maxillofacial Surgery, Department of Dentistry, Taipei-Veterans General Hospital (VGH), Taipei, Taiwan.
authors.forename: Ho-Tai
authors.initials: HT
authors.lastname: Wu
authors.forename: Shun-Yao
authors.initials: SY
authors.lastname: Ko
authors.forename: Jenny Hwai-Jen
authors.initials: JH
authors.lastname: Fong
authors.forename: Kuo-Wei
authors.initials: KW
authors.lastname: Chang
authors.forename: Tsung-Yun
authors.initials: TY
authors.lastname: Liu
authors.forename: Shou-Yen
authors.initials: SY
authors.lastname: Kao
mesh_terms: D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D016022:Case-Control Studies; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects*; D004847:Epithelial Cells / Q000201:enzymology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D007972:Leukoplakia, Oral / Q000201:enzymology; D008297:Male; D009061:Mouth Mucosa / Q000201:enzymology; D009062:Mouth Neoplasms / Q000201:enzymology*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011230:Precancerous Conditions / Q000201:enzymology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D009538:Nicotine; D051057:Proto-Oncogene Proteins c-akt