Screening and analysis of pathogenic genes during DMBA-induced buccal mucosa carcinogenesis in golden hamsters.
We designed to screen pathogenic genes related to the occurrence and development of oral buccal mucosa cancer by whole genome microarray and analyze the mechanisms of carcinogenesis. The golden hamster model of buccal mucosa cancer was established by induction with DMBA. cRNAs labeled with Cy3 were synthesized and hybridized with Agilent Whole Rat Genome Arrays containing 41,000 genes/ESTs. A Venn diagram analysis was performed to screen the continuously abnormally expressed genes. Our results show 5,255 significantly differentially expressed genes in golden hamster pouch mucosa during the progression of normal buccal mucosa to squamous cell carcinoma, of which 2,896 genes were up-regulated and 2,359 genes were down-regulated. Twenty-two genes were significantly differentially expressed at all stages of buccal mucosa carcinogenesis. Metabolism of xenobiotics by cytochrome P450 and the arachidonic acid metabolism pathway were closely related to each stage of buccal mucosa carcinogenesis. The expression changes of Eaf2, an up-regulated gene, and Ecg2, a down-regulated gene, determined by RT-PCR were consistent with the microarray. In conclusion, expression changes of various genes were involved in different stages of buccal mucosa carcinogenesis. The continuously abnormally expressed genes (Pthlh, Cyp2b13, Serpinb3, Cyp4b1, Ecg2, Btc, Krt10, Eaf2 and Trim2) at all stages of buccal mucosa carcinogenesis are important candidate genes for dynamic observation of the occurrence, development and prognosis of cancer. Searching for various effective inhibitors of xenobiotic metabolism by cytochrome P450 and the arachidonic acid metabolism pathway may suggest a therapy for the treatment and chemoprevention of oral squamous cell carcinoma.
Yang
Kai
K
Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, PR China. cqfyyk@hotmail.com
Zhang
Guodong
G
Mei
Jie
J
Chen
Dan
D
Wu
Mingjun
M
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D002273:Carcinogens / Q000633:toxicity*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D019295:Computational Biology; D006224:Cricetinae; D005260:Female; D020869:Gene Expression Profiling; D008647:Mesocricetus; D009061:Mouth Mucosa / Q000378:metabolism / Q000473:pathology*; D009062:Mouth Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D002273:Carcinogens; D012333:RNA, Messenger; D015127:9,10-Dimethyl-1,2-benzanthracene