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.

METHOD:

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.

CONCLUSION:

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: Ho-Tai Wu, Shun-Yao Ko, Jenny Hwai-Jen Fong, Kuo-Wei Chang, Tsung-Yun Liu, Shou-Yen Kao
• Journal: Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology (J Oral Pathol Med) Vol. 38 Issue 2 Pg. 206-13 (Feb 2009) ISSN: 1600-0714 [Electronic] Denmark
• PMID: 18331557 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nicotine
• Proto-Oncogene Proteins c-akt

Topics

• Blotting, Western
• Carcinoma, Squamous Cell (enzymology)
• Case-Control Studies
• Cell Line, Transformed
• Cell Line, Tumor
• Cell Transformation, Neoplastic (drug effects)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Enzyme Induction (drug effects)
• Epithelial Cells (enzymology)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Hydrogen-Ion Concentration
• Immunohistochemistry
• Leukoplakia, Oral (enzymology)
• Male
• Mouth Mucosa (enzymology)
• Mouth Neoplasms (enzymology)
• Nicotine (administration & dosage, pharmacology)
• Phosphorylation (drug effects)
• Precancerous Conditions (enzymology)
• Proto-Oncogene Proteins c-akt (metabolism)