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EpigeneticInactivation ofBetaig-h3 Gene inHuman Cancer Cells Genze ShaoJ. Gállego BerenguerAlain Borczuk2006 год

Epigenetic Inactivation of Betaig-h3 Gene in Human Cancer Cells
статья из журнала

Полный текстСтраница публикацииПубликация в OpenAlex
Аннотация: Abstract Gene silencing by CpG island methylation in the promoter region is one of the mechanisms by which tumor suppressor genes are inactivated in human cancers. It has been shown previously that Betaig-h3 gene, which encodes an extracellular matrix protein involved in cell adhesion and tumorigenesis, is down-regulated or silenced in a variety of human cancer cell lines. To unravel the underlying molecular mechanism(s) for this phenomenon, DNA methylation patterns of Betaig-h3 CpG island were examined in normal, immortalized, and cancer cell lines derived from lung, prostate, mammary, and kidney. A good correlation was observed between promoter hypermethylation and lost expression of Betaig-h3 gene, which was supported by the data that demethylation of promoter by 5-aza-2′-deoxycytidine reactivated Betaig-h3 and restored its expression in Betaig-h3-silenced tumor cell lines. This result was further substantiated by a luciferase reporter assay, showing the restoration of promoter activities and increased response to transforming growth factor-β treatment in Betaig-h3-negative 293T cells when transfected with unmethylated Betaig-h3 promoter. In contrast, activity of Betaig-h3 promoter was completely inactivated by in vitro methylation. Furthermore, CpG methylation of Betaig-h3 promoter was also shown in primary lung tumors that expressed decreased level of Betaig-h3 protein. These results suggest that promoter methylation plays a critical role in promoter silencing of the Betaig-h3 gene in human tumor cells. (Cancer Res 2006; 66(9): 4566-73)
Год издания: 2006
Авторы: Genze Shao, J. Gállego Berenguer, Alain Borczuk, Charles A. Powell, Tom K. Hei, Yongliang Zhao
Издательство: American Association for Cancer Research
Источник: Cancer Research
Ключевые слова: Epigenetics and DNA Methylation, Cancer-related gene regulation, Neonatal Respiratory Health Research
Другие ссылки: Cancer Research (PDF)
Cancer Research (HTML)
PubMed (HTML)