論文 - 詳細
| RRC ID | 42079 |
|---|---|
| 著者 | Ogasawara S, Maesawa C, Yamamoto M, Akiyama Y, Wada K, Fujisawa K, Higuchi T, Tomisawa Y, Sato N, Endo S, Saito K, Masuda T. |
| タイトル | Disruption of cell-type-specific methylation at the Maspin gene promoter is frequently involved in undifferentiated thyroid cancers. |
| ジャーナル | Oncogene |
| Abstract |
Cancer-associated DNA hypomethylation is as prevalent as cancer-linked hypermethylation, but the biological significance of DNA hypomethylation in carcinogenesis is less understood. The expression of Maspin (mammary serpin) in differentiated normal cells is regulated by epigenetic modifications in a cell-type-specific manner. Paradoxical Maspin expression due to epigenetic modification has been addressed in several cancer cell types. To elucidate the role of the Maspin gene in thyroid cancer, we studied methylation status in the promoter region and its expression in six human undifferentiated thyroid cancer cell lines and in specimens from 92 primary thyroid tumors, consisting of six follicular adenomas, 56 well-differentiated thyroid cancers (WDTCs), 17 poorly differentiated thyroid cancers (PDTCs) and 13 undifferentiated thyroid cancers (UDTCs). Three of the six cell lines overexpressed Maspin mRNA and its protein product, but the remaining three did not. The methylation status at the promoter region was inversely correlated with Maspin expression. In Maspin-negative cell lines, Maspin expression was induced by treatment with 5-aza-2'-deoxycytidine, a DNA demethylating agent. Immunoreactivity for Maspin protein was frequently detected in UDTCs (8/13, 62%) and PDTCs (7/17, 41%). Immunoreactivity for Maspin was diffusely positive in UDTCs, and was restricted to dedifferentiated components of the tumor in PDTCs. Positive immunoreactivity was infrequent in WDTCs (1/56, 2%), and all follicular adenomas and normal thyroid glands were completely negative. Their methylation status evaluated by the methylation-specific PCR method showed a good inverse correlation with their immunoreactivity in surgically resected specimens. Our data suggest that overexpression of Maspin by DNA hypomethylation is closely associated with morphological dedifferentiation in thyroid cancers. |
| 巻・号 | 23(5) |
| ページ | 1117-24 |
| 公開日 | 2004-2-5 |
| DOI | 10.1038/sj.onc.1207211 |
| PII | 1207211 |
| PMID | 14743202 |
| MeSH | Adenoma / genetics Adenoma / metabolism Azacitidine / analogs & derivatives* Azacitidine / pharmacology Cell Line, Tumor DNA Methylation* Decitabine Gene Expression Regulation, Neoplastic Genes, Tumor Suppressor Humans Promoter Regions, Genetic* Proteins / drug effects Proteins / genetics* Proteins / metabolism RNA, Messenger / analysis Serpins / drug effects Serpins / genetics* Serpins / metabolism Thyroid Gland / metabolism Thyroid Neoplasms / genetics* Thyroid Neoplasms / metabolism Thyroid Neoplasms / pathology |
| IF | 7.971 |
| 引用数 | 43 |
| WOS 分野 | GENETICS & HEREDITY ONCOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HTC/C3(RCB0452) |