Artikel
Frequently Altered Expression of Wnt Antagonists DKK Family in Ovarian Cancer
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Veröffentlicht: | 20. März 2006 |
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Gliederung
Text
The Wnt signalling pathway plays a key role in embryonic development and defects in this pathway have also been implicated in the carcinogenesis of various types of tumors. Constitutive activation of ß-catenin and increased expression of specific Wnt target genes have been found frequently in ovarian cancer. The Dkk gene family members are negative regulators of Wnt signalling pathway and Dkk-3 can function as a suppressor for human tumor growth. To delineate the role of the Dkk gene family in ovarian cancer, we examined expression of Dkk genes and ß-catenin in 30 ovarian carcinomas. Expression of Dkk genes were detected by real-time PCR. The proliferation- associated nuclear antigen Ki-67 was analysed by immunohistochemistry on histological sections. T-cell factor (TCF) regulated transcription activity was analysed by reporter assays with TEC-LEF-responsive reporter constructs in vitro. Loss and reduced expression of Dkk1, Dkk3 and Dkk4 was frequently detected in ovarian cancer samples analysed and correlates with elevated transcription activity of ß-catenin. The correlation of dkk expression with clinical and pathological parameters was discussed. The results in this study suggest that altered expression of Dkk genes could be predominant mechanisms for activation of Wnt signalling pathway in the carcinogenesis of ovarian cancer.