Aberrant WNT/β-catenin signaling in parathyroid carcinoma

Molecular Cancer

Research

Henning Dralle¹  Magnus Sundström²  Gunnar Westin³  Jessica Svedlund³  Maria Aurén³  Göran Åkerström³  Peyman Björklund³ 

[1] Department of General Surgery, Martin-Luther-University of Halle-Wittenberg, 06097, Halle/Saale, Germany;Department of Genetics and Pathology, Uppsala University, SE-751 85, Uppsala, Sweden;Department of Surgical Sciences, Endocrine Unit, Uppsala University, SE-751 85, Uppsala, Sweden;

关键词: Adenomatous Polyposis Coli;    Parathyroid Adenoma;    Decitabine;    Parathyroid Carcinoma;    Adenomatous Polyposis Coli Promoter;   

DOI  :  10.1186/1476-4598-9-294

 received in 2010-06-02, accepted in 2010-11-15,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundParathyroid carcinoma (PC) is a very rare malignancy with a high tendency to recur locally, and recurrent disease is difficult to eradicate. In most western European countries and United States, these malignant neoplasms cause less than 1% of the cases with primary hyperparathyroidism, whereas incidence as high as 5% have been reported from Italy, Japan, and India. The molecular etiology of PC is poorly understood.ResultsThe APC (adenomatous polyposis coli) tumor suppressor gene was inactivated by DNA methylation in five analyzed PCs, as determined by RT-PCR, Western blotting, and quantitative bisulfite pyrosequencing analyses. This was accompanied by accumulation of stabilized active nonphosphorylated β-catenin, strongly suggesting aberrant activation of the WNT/β-catenin signaling pathway in these tumors. Treatment of a primary PC cell culture with the DNA hypomethylating agent 5-aza-2'-deoxycytidine (decitabine, Dacogen(r)) induced APC expression, reduced active nonphosphorylated β-catenin, inhibited cell growth, and caused apoptosis.ConclusionAberrant WNT/β-catenin signaling by lost expression and DNA methylation of APC, and accumulation of active nonphosphorylated β-catenin was observed in the analyzed PCs. We suggest that adjuvant epigenetic therapy should be considered as an additional option in the treatment of patients with recurrent or metastatic parathyroid carcinoma.

【 授权许可】

Unknown   
© Svedlund et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.