Downregulation of Ches1 and other novel genes in oral cancer cells chronically exposed to areca nut extract.
BACKGROUND
This study was undertaken to identify the genes in response to areca nut extract, a potential carcinogen of oral cancer.


METHODS
Two oral cancer sublines chronically treated with areca nut extract were established. Methods such as microarray and immunohistochemistry were used to screen and validate the genes' altered expressions in areca nut extract-sublines or in cancer tissues.


RESULTS
A total of 35 genes were differentially expressed in both sublines. Several functional pathways were significantly altered. Six genes were confirmed over 2-fold of changes, including Ches1. Functional analyses showed that overexpression of Ches1 suppressed cell growth and arrested cells in the G2/M phase. Consistently, this gene has reduced expression in 52% of oral cancer tissues, which was significantly correlated with the areca nut chewing habit of patients (p = .04).


CONCLUSIONS
We identified 35 candidates and validated 6 genes that may be associated with areca nut-induced oral cancer. Loss of Ches1 may be attributed to areca nut extract-induced oral carcinogenesis.
Chen
Yin-Ju
YJ
Graduate School of Medical Biotechnology, Chang Gung University, Taoyuan 333, Taiwan, Providence of China.
Liao
Chun-Ta
CT
Chen
Po-Jen
PJ
Lee
Li-Yu
LY
Li
Yi-Chen
YC
Chen
I-How
IH
Wang
Hung-Ming
HM
Chang
Joseph T
JT
Chen
Li-Ju
LJ
Yen
Tzu-Chen
TC
Tang
Chuan-Yi
CY
Cheng
Ann-Joy
AJ
D001114:Areca; D014408:Biomarkers, Tumor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D051858:Forkhead Transcription Factors; D005796:Genes / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008409:Mastication / Q000187:drug effects; D008875:Middle Aged; D009061:Mouth Mucosa / Q000187:drug effects; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D008517:Phytotherapy / Q000009:adverse effects*; D010936:Plant Extracts / Q000633:toxicity*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040081:Protein Array Analysis; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C106158:FOXN3 protein, human; D051858:Forkhead Transcription Factors; D010936:Plant Extracts; D012097:Repressor Proteins