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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.1
- 수록면
- 45 - 53 (9page)
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Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes (SFRP2, SFRP4, SFRP5, DKK1, DKK2, and APC) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2, SFRP4, DKK1, and DKK2 was significantly increased in gastric cancer. Moreover, concurrent hypermethylation of SFRP2 and DKK2 was observed in gastric cancer and this was significantly associated with increased expression of ?-catenin, indicating that the joint inactivation of these two genes promoted the activation of the Wnt signaling pathway. Further analysis using a multivariate Cox proportional hazards model showed that DKK2 methylation was an independent prognostic factor for poor overall survival, and the predictive value was markedly enhanced when the combined methylation status of SFRP2 and DKK2 was con-sidered. In addition, the methylation level of SFRP4 and DKK2 was correlated with the patient’s age and tumor differentiation, respectively. In conclusion, epigenetic silencing of Wnt antagonists was associated with gastric carcinogenesis, and concurrent hypermethylation of SFRP2 and DKK2 could be a potential marker for a prognosis of poor overall survival.
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참고문헌 (28)
참고문헌 신청
Behrens, J. / 1996 / Functional interaction of beta-catenin with the transcription factor LEF-1 / Nature 382:638~642
Cadigan, K. M. / 1997 / Wnt signaling : a common theme in animal development / Genes Dev. 11:3286~3305
Cheng, Y. Y. / 2007 / Frequent epigenetic inactivation of secreted frizzled-related protein 2 (SFRP2) by promoter methylation in human gastric cancer / Br. J. Cancer 97:895~901
Clements, W. M. / 2002 / beta-Catenin mutation is a frequent cause of Wnt pathway activation in gastric cancer / Cancer Res. 62:3503~3506
Ferlay, J. / 2010 / Estimates of worldwide burden of cancer in 2008:GLOBOCAN 2008 / Int. J. Cancer 127:2893~2917
Cadigan, K. M. / 1997 / Wnt signaling : a common theme in animal development / Genes Dev. 11:3286~3305
Cheng, Y. Y. / 2007 / Frequent epigenetic inactivation of secreted frizzled-related protein 2 (SFRP2) by promoter methylation in human gastric cancer / Br. J. Cancer 97:895~901
Clements, W. M. / 2002 / beta-Catenin mutation is a frequent cause of Wnt pathway activation in gastric cancer / Cancer Res. 62:3503~3506
Ferlay, J. / 2010 / Estimates of worldwide burden of cancer in 2008:GLOBOCAN 2008 / Int. J. Cancer 127:2893~2917
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