Hypermethylation of the p16 gene promoter in ptergia and its association with the expression of DNA methyltransferase 3b

Pei Liang Chen, Ya Wen Cheng, Chun Chi Chiang, Sung Huei Tseng, Pak Sam Chau, Yi Yu Tsai

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Purpose: A pterygium has long been considered as a degenerative condition. After p53 protein was found to be abnormally expressed in the epithelium, researchers suggested that a pterygium may be a tumor, but additional evidence is required to support this hypothesis. Aberrant methylation of the p16 gene (CDKN2A) promoter and resultant gene silencing play important roles in the pathogenesis of many types of human cancers. The purpose of this study was to investigate hypermethylation of the p16 promoter in pterygia and the relationship between this hypermethylation and the expression of p16 and DNA methyltransferase 3b (DNMT3b) proteins. Methods: We studied the methylation status of p16 and the expression of p16 and DNMT3b proteins by performing methylation-specific polymerase chain reaction and immunohistochemistry, respectively, in specimens of 129 pterygia and 16 normal conjunctiva. The results were statistically analyzed. Results: Hypermethylation of the p16 gene promoter was detected in 21 (16.3%) of 129 pterygial specimens. Among them, 46 (35.7%) were positive for p16 protein expression, and 83 (64.3%) were negative. Staining for p16 was limited to the nuclei of the epithelial layer. We observed a significant reverse correlation between hypermethylation of the p16 promoter and the expression of p16 protein (p=0.006). Thirty-eight (29.5%) pterygial specimens were positive for DNMT3b protein expression, and 91 (70.5%) were negative. DNMT3b staining was limited to the nuclei of the epithelia] layer. A significant correlation was found between hypermethylation of the p16 promoter and the expression of DNMT3b protein (P<0.001). Conclusions: The p16 gene promoter was hypermethylated in pterygia, and this hypermethylation was strongly linked to expression of the positive expression of DNMT3b protein and to the suppression of p16 protein. These data provided molecular evidence that methylation occurs in pterygia and that it may play a role in the their development. © 2006 Molecular Vision.

Original languageEnglish
Pages (from-to)1411-1416
Number of pages6
JournalMolecular Vision
Volume12
Publication statusPublished - Nov 17 2006
Externally publishedYes

Fingerprint

p16 Genes
Pterygium
Methylation
Proteins
Epithelium
Staining and Labeling
DNA methyltransferase 3B
Conjunctiva
Gene Silencing
Neoplasms
Immunohistochemistry
Research Personnel
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Chen, P. L., Cheng, Y. W., Chiang, C. C., Tseng, S. H., Chau, P. S., & Tsai, Y. Y. (2006). Hypermethylation of the p16 gene promoter in ptergia and its association with the expression of DNA methyltransferase 3b. Molecular Vision, 12, 1411-1416.

Hypermethylation of the p16 gene promoter in ptergia and its association with the expression of DNA methyltransferase 3b. / Chen, Pei Liang; Cheng, Ya Wen; Chiang, Chun Chi; Tseng, Sung Huei; Chau, Pak Sam; Tsai, Yi Yu.

In: Molecular Vision, Vol. 12, 17.11.2006, p. 1411-1416.

Research output: Contribution to journalArticle

Chen, PL, Cheng, YW, Chiang, CC, Tseng, SH, Chau, PS & Tsai, YY 2006, 'Hypermethylation of the p16 gene promoter in ptergia and its association with the expression of DNA methyltransferase 3b', Molecular Vision, vol. 12, pp. 1411-1416.
Chen, Pei Liang ; Cheng, Ya Wen ; Chiang, Chun Chi ; Tseng, Sung Huei ; Chau, Pak Sam ; Tsai, Yi Yu. / Hypermethylation of the p16 gene promoter in ptergia and its association with the expression of DNA methyltransferase 3b. In: Molecular Vision. 2006 ; Vol. 12. pp. 1411-1416.
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abstract = "Purpose: A pterygium has long been considered as a degenerative condition. After p53 protein was found to be abnormally expressed in the epithelium, researchers suggested that a pterygium may be a tumor, but additional evidence is required to support this hypothesis. Aberrant methylation of the p16 gene (CDKN2A) promoter and resultant gene silencing play important roles in the pathogenesis of many types of human cancers. The purpose of this study was to investigate hypermethylation of the p16 promoter in pterygia and the relationship between this hypermethylation and the expression of p16 and DNA methyltransferase 3b (DNMT3b) proteins. Methods: We studied the methylation status of p16 and the expression of p16 and DNMT3b proteins by performing methylation-specific polymerase chain reaction and immunohistochemistry, respectively, in specimens of 129 pterygia and 16 normal conjunctiva. The results were statistically analyzed. Results: Hypermethylation of the p16 gene promoter was detected in 21 (16.3{\%}) of 129 pterygial specimens. Among them, 46 (35.7{\%}) were positive for p16 protein expression, and 83 (64.3{\%}) were negative. Staining for p16 was limited to the nuclei of the epithelial layer. We observed a significant reverse correlation between hypermethylation of the p16 promoter and the expression of p16 protein (p=0.006). Thirty-eight (29.5{\%}) pterygial specimens were positive for DNMT3b protein expression, and 91 (70.5{\%}) were negative. DNMT3b staining was limited to the nuclei of the epithelia] layer. A significant correlation was found between hypermethylation of the p16 promoter and the expression of DNMT3b protein (P<0.001). Conclusions: The p16 gene promoter was hypermethylated in pterygia, and this hypermethylation was strongly linked to expression of the positive expression of DNMT3b protein and to the suppression of p16 protein. These data provided molecular evidence that methylation occurs in pterygia and that it may play a role in the their development. {\circledC} 2006 Molecular Vision.",
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AU - Chen, Pei Liang

AU - Cheng, Ya Wen

AU - Chiang, Chun Chi

AU - Tseng, Sung Huei

AU - Chau, Pak Sam

AU - Tsai, Yi Yu

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N2 - Purpose: A pterygium has long been considered as a degenerative condition. After p53 protein was found to be abnormally expressed in the epithelium, researchers suggested that a pterygium may be a tumor, but additional evidence is required to support this hypothesis. Aberrant methylation of the p16 gene (CDKN2A) promoter and resultant gene silencing play important roles in the pathogenesis of many types of human cancers. The purpose of this study was to investigate hypermethylation of the p16 promoter in pterygia and the relationship between this hypermethylation and the expression of p16 and DNA methyltransferase 3b (DNMT3b) proteins. Methods: We studied the methylation status of p16 and the expression of p16 and DNMT3b proteins by performing methylation-specific polymerase chain reaction and immunohistochemistry, respectively, in specimens of 129 pterygia and 16 normal conjunctiva. The results were statistically analyzed. Results: Hypermethylation of the p16 gene promoter was detected in 21 (16.3%) of 129 pterygial specimens. Among them, 46 (35.7%) were positive for p16 protein expression, and 83 (64.3%) were negative. Staining for p16 was limited to the nuclei of the epithelial layer. We observed a significant reverse correlation between hypermethylation of the p16 promoter and the expression of p16 protein (p=0.006). Thirty-eight (29.5%) pterygial specimens were positive for DNMT3b protein expression, and 91 (70.5%) were negative. DNMT3b staining was limited to the nuclei of the epithelia] layer. A significant correlation was found between hypermethylation of the p16 promoter and the expression of DNMT3b protein (P<0.001). Conclusions: The p16 gene promoter was hypermethylated in pterygia, and this hypermethylation was strongly linked to expression of the positive expression of DNMT3b protein and to the suppression of p16 protein. These data provided molecular evidence that methylation occurs in pterygia and that it may play a role in the their development. © 2006 Molecular Vision.

AB - Purpose: A pterygium has long been considered as a degenerative condition. After p53 protein was found to be abnormally expressed in the epithelium, researchers suggested that a pterygium may be a tumor, but additional evidence is required to support this hypothesis. Aberrant methylation of the p16 gene (CDKN2A) promoter and resultant gene silencing play important roles in the pathogenesis of many types of human cancers. The purpose of this study was to investigate hypermethylation of the p16 promoter in pterygia and the relationship between this hypermethylation and the expression of p16 and DNA methyltransferase 3b (DNMT3b) proteins. Methods: We studied the methylation status of p16 and the expression of p16 and DNMT3b proteins by performing methylation-specific polymerase chain reaction and immunohistochemistry, respectively, in specimens of 129 pterygia and 16 normal conjunctiva. The results were statistically analyzed. Results: Hypermethylation of the p16 gene promoter was detected in 21 (16.3%) of 129 pterygial specimens. Among them, 46 (35.7%) were positive for p16 protein expression, and 83 (64.3%) were negative. Staining for p16 was limited to the nuclei of the epithelial layer. We observed a significant reverse correlation between hypermethylation of the p16 promoter and the expression of p16 protein (p=0.006). Thirty-eight (29.5%) pterygial specimens were positive for DNMT3b protein expression, and 91 (70.5%) were negative. DNMT3b staining was limited to the nuclei of the epithelia] layer. A significant correlation was found between hypermethylation of the p16 promoter and the expression of DNMT3b protein (P<0.001). Conclusions: The p16 gene promoter was hypermethylated in pterygia, and this hypermethylation was strongly linked to expression of the positive expression of DNMT3b protein and to the suppression of p16 protein. These data provided molecular evidence that methylation occurs in pterygia and that it may play a role in the their development. © 2006 Molecular Vision.

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