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Genome-wide analysis of gene expression changes in mouse tongue squamous cell carcinomas induced by 4-nitroquinoline 1-oxide (4-NQO)

ABSTRACT: We hypothesized that the expression of many genes are dysregulated during oral cancer carcinogenesis. We examined genome-wide transcript levels in normal mouse tongues and the tongue squamous cell carcinomas induced by 4-NQO. The results will provide important information for the diagnosis, prevention, and treatment of human oral cancers, including tongue cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE54246 | GEO | 2014/07/01

SECONDARY ACCESSION(S): PRJNA236032

REPOSITORIES: GEO

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Genome-wide analysis of gene expression changes in mouse tongue squamous cell carcinomas induced by 4-nitroquinoline 1-oxide (4-NQO)

Project description:We hypothesized that the expression of many genes are dysregulated during oral cancer carcinogenesis. We examined genome-wide transcript levels in normal mouse tongues and the tongue squamous cell carcinomas induced by 4-NQO. The results will provide important information for the diagnosis, prevention, and treatment of human oral cancers, including tongue cancer. Total RNA obtained from normal tongues (not treated with 4-NQO) and tongue squamous cell carcinomas induced by 4-NQO.

2014-07-01 | E-GEOD-54246 | biostudies-arrayexpress

Expression data of tongue mucosa from normal mice and mice treated by the 4-NQO

Project description:A better understanding of molecular changes during oral tumorigenesis may help defining new personalized prevention strategies. In order to test this hypothesis, we analyzed whole-genome expression changes in a murine model of oral carcinogenesis, induced by an oral carcinogen (4-NQO) We generated genome-wide expression profiles of microdissected cells from murine tongue at each step of oral tumorigenesis: normal mucosa, hyperplasia, dysplasia and tumor.

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Genome-wide changes in transcript levels in tongues after 4-NQO and ethanol treatment

Project description:Tobacco use and alcohol consumption are two major contributing factors for head and neck squamous cell carcinoma (HNSCC) carcinogenesis. We combined the 4-nitroquinoline-1-oxide (4-NQO) oral carcinogenesis mouse model and the Meadows-Cook alcohol mouse models and performed next generation genome-wide RNA-sequencing of tongues. We determined changes in transcript levels in four groups: 4-NQO followed by ethanol treatment (4-NQO/EtOH), 4-NQO followed by normal drinking water (4-NQO/Untr.), vehicle control followed by ethanol treatment (V.C./EtOH), and vehicle control followed by normal drinking water (V.C./Untr.). We found that the 494 gene transcripts were significantly changed (at least a 2-fold change where p<0.05) in the V.C./EtOH group compared to the V.C./Untr. group. The 4-NQO/Untr. group had 1,808 transcripts significantly changed compared to the V.C./Untr group, while the 4-NQO/EtOH group had 3,606 significantly changed transcripts as compared to the V.C/Untr. group. This study is the first to show that 4-NQO followed by ethanol cause the largest number of changes in transcript levels in the tongue.

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Molecular characterization of 4-NQO induced F344 rat tongue carcinogenesis: alteration of multiple gene expression and hypomethylation of PTGS2 proximal promoter

Project description:The 4-NQO induced rat tongue carcinogenesis model presenting considerable histologic and molecular similarity to oral cancers commonly seen in humans is very useful for investigating oral carcinogenesis. In order to understand the molecular basis of oral carcinogenesis and identify gene biomarkers and potential chemopreventive targets for future studies, we characterized the molecular changes in oral squamous cell carcinoma (SCC) samples generated from this model system using F344 rats by performing gene expression microarray and methylation analysis of selected genes. Microarray studies identified 1735 genes to be upregulated by at least 2 fold (p<0.05, n=11) and 1803 genes to be downregulated by at least 50% (p<0.05, n=11) in SCC in comparison to the adjacent normal tissues and 28 KEGG pathways to be altered in SCC (p<0.01). Among the altered genes, keratins and keratin associated proteins were found to be differentially regulated and the keratin profile appeared to an important biomarker for oral SCC. PTGS2 and PTGS2 relevant genes, which are potential targets of chemoprevention and therapy, were also found to be upregulated in SCC and confirmed by qRT-PCR. The upregulation of PTGS2 appeared to correlate with hypomethylation of its proximal promoter. Methylation analysis of other selected genes showed that the first exon of APC2 was methylated in normal tissues, and the methylation level increased moderately in SCC samples (p<0.01, n=8). These results demonstrate that 4-NQO induced tongue carcinogenesis in F344 rats is accompanied by alteration of multiple gene expression, hypomethylation of PTGS2 and increased methylation of APC2. Gene expression in untreated normal vs.4-NQO induced tongue tumors in F344 rats (n=11).

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Molecular characterization of 4-NQO induced F344 rat tongue carcinogenesis: alteration of multiple gene expression and hypomethylation of PTGS2 proximal promoter

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A minimal DNA 5-methylcytosine signature of oral tongue squamous cell carcinoma [methylation]

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