Frequent epigenetic inactivation of RASSF2 in thyroid cancer and functional consequences
| Autor: | Reinhard Dammann, Undraga Schagdarsurengin, Katrin Steinmann, Antje M. Richter, Cornelia Lange, Juliane Hornung |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Cancer Research endocrine system Goiter Adenoma endocrine system diseases Apoptosis Biology In Vitro Techniques Protein Serine-Threonine Kinases medicine.disease_cause lcsh:RC254-282 Serine-Threonine Kinase 3 Cell Line Thyroid carcinoma Cell Line Tumor Two-Hybrid System Techniques medicine Humans Thyroid Neoplasms Promoter Regions Genetic Thyroid cancer Aged Cell Proliferation Research Tumor Suppressor Proteins Thyroid Intracellular Signaling Peptides and Proteins Methylation DNA Methylation Middle Aged medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.anatomical_structure Oncology DNA methylation Cancer research Molecular Medicine Female Carcinogenesis Protein Binding |
| Zdroj: | Molecular Cancer Molecular Cancer, Vol 9, Iss 1, p 264 (2010) |
| ISSN: | 1476-4598 |
| Popis: | Background The Ras association domain family (RASSF) encodes for distinct tumor suppressors and several members are frequently silenced in human cancer. In our study, we analyzed the role of RASSF2, RASSF3, RASSF4, RASSF5A, RASSF5C and RASSF6 and the effectors MST1, MST2 and WW45 in thyroid carcinogenesis. Results Frequent methylation of the RASSF2 and RASSF5A CpG island promoters in thyroid tumors was observed. RASSF2 was methylated in 88% of thyroid cancer cell lines and in 63% of primary thyroid carcinomas. RASSF2 methylation was significantly increased in primary thyroid carcinoma compared to normal thyroid, goiter and follicular adenoma (0%, 17% and 0%, respectively; p < 0.05). Patients which were older than 60 years were significantly hypermethylated for RASSF2 in their primary thyroid tumors compared to those younger than 40 years (90% vs. 38%; p < 0.05). RASSF2 promoter hypermethylation correlated with its reduced expression and treatment with a DNA methylation inhibitor reactivated RASSF2 transcription. Over-expression of RASSF2 reduced colony formation of thyroid cancer cells. Functionally our data show that RASSF2 interacts with the proapoptotic kinases MST1 and MST2 and induces apoptosis in thyroid cancer cell lines. Deletion of the MST interaction domain of RASSF2 reduced apoptosis significantly (p < 0.05). Conclusion These results suggest that RASSF2 encodes a novel epigenetically inactivated candidate tumor suppressor gene in thyroid carcinogenesis. |
| Databáze: | OpenAIRE |
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