論文 - 詳細
| RRC ID | 42562 |
|---|---|
| 著者 | Lombaerts M, van Wezel T, Philippo K, Dierssen JW, Zimmerman RM, Oosting J, van Eijk R, Eilers PH, van de Water B, Cornelisse CJ, Cleton-Jansen AM. |
| タイトル | E-cadherin transcriptional downregulation by promoter methylation but not mutation is related to epithelial-to-mesenchymal transition in breast cancer cell lines. |
| ジャーナル | Br J Cancer |
| Abstract |
Using genome-wide expression profiling of a panel of 27 human mammary cell lines with different mechanisms of E-cadherin inactivation, we evaluated the relationship between E-cadherin status and gene expression levels. Expression profiles of cell lines with E-cadherin (CDH1) promoter methylation were significantly different from those with CDH1 expression or, surprisingly, those with CDH1 truncating mutations. Furthermore, we found no significant differentially expressed genes between cell lines with wild-type and mutated CDH1. The expression profile complied with the fibroblastic morphology of the cell lines with promoter methylation, suggestive of epithelial-mesenchymal transition (EMT). All other lines, also the cases with CDH1 mutations, had epithelial features. Three non-tumorigenic mammary cell lines derived from normal breast epithelium also showed CDH1 promoter methylation, a fibroblastic phenotype and expression profile. We suggest that CDH1 promoter methylation, but not mutational inactivation, is part of an entire programme, resulting in EMT and increased invasiveness in breast cancer. The molecular events that are part of this programme can be inferred from the differentially expressed genes and include genes from the TGFbeta pathway, transcription factors involved in CDH1 regulation (i.e. ZFHX1B, SNAI2, but not SNAI1, TWIST), annexins, AP1/2 transcription factors and members of the actin and intermediate filament cytoskeleton organisation. |
| 巻・号 | 94(5) |
| ページ | 661-71 |
| 公開日 | 2006-3-13 |
| DOI | 10.1038/sj.bjc.6602996 |
| PII | 6602996 |
| PMID | 16495925 |
| PMC | PMC2361216 |
| MeSH | Breast Neoplasms / pathology* Cadherins / biosynthesis* Cell Line, Tumor Cell Transformation, Neoplastic DNA Methylation* DNA Mutational Analysis Down-Regulation Epithelial Cells Female Gene Expression Profiling* Gene Expression Regulation, Neoplastic Humans Mesoderm / cytology Neoplasm Invasiveness Polymerase Chain Reaction Promoter Regions, Genetic Transcription, Genetic Transforming Growth Factor beta / physiology |
| IF | 5.791 |
| 引用数 | 229 |
| WOS 分野 | ONCOLOGY |
| 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 | 15 |
| 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 | OCUB-F(RCB0882) |