論文 - 詳細
| RRC ID | 1426 |
|---|---|
| 著者 | Kikuchi S, Yamada D, Fukami T, Masuda M, Sakurai-Yageta M, Williams YN, Maruyama T, Asamura H, Matsuno Y, Onizuka M, Murakami Y. |
| タイトル | Promoter methylation of DAL-1/4.1B predicts poor prognosis in non-small cell lung cancer. |
| ジャーナル | Clin Cancer Res |
| Abstract |
PURPOSE:DAL-1/4.1B is an actin-binding protein originally identified as a molecule whose expression is down-regulated in lung adenocarcinoma. We have previously shown that a lung tumor suppressor, TSLC1, associates with DAL-1, suggesting that both proteins act in the same cascade. The purpose of this study is to understand the molecular mechanisms and clinical significance of DAL-1 inactivation in lung cancer. EXPERIMENTAL DESIGN:We studied aberration of the DAL-1 in 103 primary non-small cell lung cancers (NSCLC) and 18 lung cancer cells. Expression and allelic and methylation status of DAL-1 was examined by reverse transcription-PCR, microsatellite analysis, and bisulfite sequencing or bisulfite single-strand conformational polymorphism, respectively. RESULTS:Loss of DAL-1 expression was strongly correlated with promoter methylation in lung cancer cells, whereas DAL-1 expression was restored by a demethylating agent, 5-aza-2'-deoxycytidine. The DAL-1 promoter was methylated in 59 (57%) primary NSCLC tumors, 37% of which were associated with loss of heterozygosity around the DAL-1 on chromosomal region 18p11.3. In squamous cell carcinomas, DAL-1 methylation was observed in 9 of 10 tumors at stage I, whereas the incidence of methylation gradually increased in adenocarcinomas as they progressed [13 of 36 (36%), 4 of 12 (33%), 14 of 17 (82%), and 3 of 3 (100%) tumors at stages I, II, III, and IV, respectively; P = 0.0026]. Furthermore, in adenocarcinomas, disease-free survival and overall survival were significantly shorter in patients with tumors harboring the methylated DAL-1 (P = 0.0011 and P = 0.045, respectively). CONCLUSIONS:DAL-1 methylation is involved in the development and progression of NSCLC and provides an indicator for poor prognosis. |
| 巻・号 | 11(8) |
| ページ | 2954-61 |
| 公開日 | 2005-4-15 |
| DOI | 10.1158/1078-0432.CCR-04-2206 |
| PII | 11/8/2954 |
| PMID | 15837747 |
| MeSH | Aged Carcinoma, Non-Small-Cell Lung / genetics Carcinoma, Non-Small-Cell Lung / pathology* Cell Line, Tumor Chromosomes, Human, Pair 18 / genetics CpG Islands / genetics DNA Methylation* DNA, Neoplasm / chemistry DNA, Neoplasm / genetics DNA, Neoplasm / metabolism Humans Loss of Heterozygosity Lung Neoplasms / genetics Lung Neoplasms / pathology* Membrane Proteins / genetics* Microfilament Proteins Mitotic Index Polymorphism, Single-Stranded Conformational Prognosis Promoter Regions, Genetic / genetics* Sequence Analysis, DNA Survival Analysis Tumor Suppressor Proteins / genetics* |
| IF | 10.107 |
| 引用数 | 50 |
| WOS 分野 | ONCOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | A549(RCB0098) PC-14(RCB0446) |