Expression of phosphorylated Akt in oral carcinogenesis and its induction by nicotine and alkaline stimulation.
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.
Wu
Ho-Tai
HT
Oral & Maxillofacial Surgery, Department of Dentistry, Taipei-Veterans General Hospital (VGH), Taipei, Taiwan.
Ko
Shun-Yao
SY
Fong
Jenny Hwai-Jen
JH
Chang
Kuo-Wei
KW
Liu
Tsung-Yun
TY
Kao
Shou-Yen
SY
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*
D009538:Nicotine; D051057:Proto-Oncogene Proteins c-akt