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Methylation-associated gene silencing of RARB in areca carcinogens induced mouse oral squamous cell carcinoma.

Lai ZL, Tsou YA, Fan SR, Tsai MH, Chen HL, Chang NW, Cheng JC, Chen CM - Biomed Res Int (2014)

Bottom Line: These results showed that retinoic acid receptor β (RARB) was indicated in hypermethylation at the promoter region and the loss of expression during cancer development.According to the results of real-time PCR, it was shown that de novo DNA methyltransferases were involved in gene epigenetic alternations of OSCC.Collectively, our results showed that RARB hypermethylation was involved in the areca-associated oral carcinogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, No. 250 Kao-Kuang Road, Taichung 402, Taiwan.

ABSTRACT
Regarding oral squamous cell carcinoma (OSCC) development, chewing areca is known to be a strong risk factor in many Asian cultures. Therefore, we established an OSCC induced mouse model by 4-nitroquinoline-1-oxide (4-NQO), or arecoline, or both treatments, respectively. These are the main two components of the areca nut that could increase the occurrence of OSCC. We examined the effects with the noncommercial MCGI (mouse CpG islands) microarray for genome-wide screening the DNA methylation aberrant in induced OSCC mice. The microarray results showed 34 hypermethylated genes in 4-NQO plus arecoline induced OSCC mice tongue tissues. The examinations also used methylation-specific polymerase chain reaction (MS-PCR) and bisulfite sequencing to realize the methylation pattern in collected mouse tongue tissues and human OSCC cell lines of different grades, respectively. These results showed that retinoic acid receptor β (RARB) was indicated in hypermethylation at the promoter region and the loss of expression during cancer development. According to the results of real-time PCR, it was shown that de novo DNA methyltransferases were involved in gene epigenetic alternations of OSCC. Collectively, our results showed that RARB hypermethylation was involved in the areca-associated oral carcinogenesis.

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Related in: MedlinePlus

The progression of mouse model development for OSCC. (a) The ratio of carcinogenesis in mouse OSCC model. There were three treatments, 4-NQO/arecoline, 4-NQO, and arecoline. Mice were sacrificed at weeks 8, 12, 14, 18, 20, 26, and 28, respectively. The scoring criteria for mouse OSCC model are described in Section 2. (b) OSCC tongue tissues with tumors were excised, fixed, embedded, and sectioned for H&E staining. The mice that were treated with 4-NQO + arecoline would induce more serious OSCC formation than 4-NQO only and arecoline only. The order of severity was followed the time of treatment.
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fig1: The progression of mouse model development for OSCC. (a) The ratio of carcinogenesis in mouse OSCC model. There were three treatments, 4-NQO/arecoline, 4-NQO, and arecoline. Mice were sacrificed at weeks 8, 12, 14, 18, 20, 26, and 28, respectively. The scoring criteria for mouse OSCC model are described in Section 2. (b) OSCC tongue tissues with tumors were excised, fixed, embedded, and sectioned for H&E staining. The mice that were treated with 4-NQO + arecoline would induce more serious OSCC formation than 4-NQO only and arecoline only. The order of severity was followed the time of treatment.

Mentions: To evaluate the efficiency of mouse model involving cotreating with arecoline and 4-NQO that mimic the etiology for OSCC tumor growth, the percentage of mice exhibiting carcinogenesis was calculated in Figure 1(a). Tumor development was assessed when treated with 4-NQO (N) and 4-NQO plus arecoline (NA) but not in arecoline. Mice were also sacrificed at 18, 26, and 28 weeks, and tongues with tumors were excised, fixed, embedded, and sectioned for H&E staining (Figure 1(b)). The H&E staining also showed that the tumor progresses were dealing with time and according to the treatments. According to the results, the incidence of tongue carcinogenesis in NA group was significantly higher than N group and arecoline group. Taken together, the treatment of NA at week 28 was much more serious than other weeks. These results suggest that arecoline promotes 4-NQO carcinogenesis in damaged oral epithelia cells.


Methylation-associated gene silencing of RARB in areca carcinogens induced mouse oral squamous cell carcinoma.

Lai ZL, Tsou YA, Fan SR, Tsai MH, Chen HL, Chang NW, Cheng JC, Chen CM - Biomed Res Int (2014)

The progression of mouse model development for OSCC. (a) The ratio of carcinogenesis in mouse OSCC model. There were three treatments, 4-NQO/arecoline, 4-NQO, and arecoline. Mice were sacrificed at weeks 8, 12, 14, 18, 20, 26, and 28, respectively. The scoring criteria for mouse OSCC model are described in Section 2. (b) OSCC tongue tissues with tumors were excised, fixed, embedded, and sectioned for H&E staining. The mice that were treated with 4-NQO + arecoline would induce more serious OSCC formation than 4-NQO only and arecoline only. The order of severity was followed the time of treatment.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150525&req=5

fig1: The progression of mouse model development for OSCC. (a) The ratio of carcinogenesis in mouse OSCC model. There were three treatments, 4-NQO/arecoline, 4-NQO, and arecoline. Mice were sacrificed at weeks 8, 12, 14, 18, 20, 26, and 28, respectively. The scoring criteria for mouse OSCC model are described in Section 2. (b) OSCC tongue tissues with tumors were excised, fixed, embedded, and sectioned for H&E staining. The mice that were treated with 4-NQO + arecoline would induce more serious OSCC formation than 4-NQO only and arecoline only. The order of severity was followed the time of treatment.
Mentions: To evaluate the efficiency of mouse model involving cotreating with arecoline and 4-NQO that mimic the etiology for OSCC tumor growth, the percentage of mice exhibiting carcinogenesis was calculated in Figure 1(a). Tumor development was assessed when treated with 4-NQO (N) and 4-NQO plus arecoline (NA) but not in arecoline. Mice were also sacrificed at 18, 26, and 28 weeks, and tongues with tumors were excised, fixed, embedded, and sectioned for H&E staining (Figure 1(b)). The H&E staining also showed that the tumor progresses were dealing with time and according to the treatments. According to the results, the incidence of tongue carcinogenesis in NA group was significantly higher than N group and arecoline group. Taken together, the treatment of NA at week 28 was much more serious than other weeks. These results suggest that arecoline promotes 4-NQO carcinogenesis in damaged oral epithelia cells.

Bottom Line: These results showed that retinoic acid receptor β (RARB) was indicated in hypermethylation at the promoter region and the loss of expression during cancer development.According to the results of real-time PCR, it was shown that de novo DNA methyltransferases were involved in gene epigenetic alternations of OSCC.Collectively, our results showed that RARB hypermethylation was involved in the areca-associated oral carcinogenesis.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, No. 250 Kao-Kuang Road, Taichung 402, Taiwan.

ABSTRACT
Regarding oral squamous cell carcinoma (OSCC) development, chewing areca is known to be a strong risk factor in many Asian cultures. Therefore, we established an OSCC induced mouse model by 4-nitroquinoline-1-oxide (4-NQO), or arecoline, or both treatments, respectively. These are the main two components of the areca nut that could increase the occurrence of OSCC. We examined the effects with the noncommercial MCGI (mouse CpG islands) microarray for genome-wide screening the DNA methylation aberrant in induced OSCC mice. The microarray results showed 34 hypermethylated genes in 4-NQO plus arecoline induced OSCC mice tongue tissues. The examinations also used methylation-specific polymerase chain reaction (MS-PCR) and bisulfite sequencing to realize the methylation pattern in collected mouse tongue tissues and human OSCC cell lines of different grades, respectively. These results showed that retinoic acid receptor β (RARB) was indicated in hypermethylation at the promoter region and the loss of expression during cancer development. According to the results of real-time PCR, it was shown that de novo DNA methyltransferases were involved in gene epigenetic alternations of OSCC. Collectively, our results showed that RARB hypermethylation was involved in the areca-associated oral carcinogenesis.

Show MeSH
Related in: MedlinePlus