論文 - 詳細
| RRC ID | 32720 |
|---|---|
| 著者 | Lu TL, Chen CM. |
| タイトル | Differential requirements for β-catenin in murine prostate cancer originating from basal versus luminal cells. |
| ジャーナル | J Pathol |
| Abstract |
A driver mutation occurring in different cells of origin may impact cancer progression differently. Previously, we demonstrated higher invasiveness in Pten-deficient prostate cancer (CaP) arising from basal cells compared to that arising from luminal cells in mice. Here, we show higher expression of epithelial-mesenchymal transition (EMT)-inducing transcription factors and stem/progenitor properties in basal-derived CaP compared to luminal-derived CaP. We further explore the requirement for β-catenin in basal and luminal prostate cells during CaP progression. Genetic ablation and pharmacological inhibition of β-catenin specifically suppress basal-derived CaP progression through reduction of stemness and cell proliferation and increased γH2Ax-associated apoptosis. Lineage tracing revealed that loss of β-catenin in basal cells impairs basal-to-luminal differentiation; conversely, β-catenin loss is dispensable for luminal-derived CaP progression. Our findings suggest that β-catenin is required for basal-derived normal luminal cells and cancer cells, but not for luminal derivatives. Although the cellular origin of CaP in patients cannot be easily determined at present, the results imply that β-catenin inhibition is a potential therapeutic option for a subset of patients with basal-derived CaP. |
| 巻・号 | 236(3) |
| ページ | 290-301 |
| 公開日 | 2015-7-1 |
| DOI | 10.1002/path.4521 |
| PMID | 25712462 |
| MeSH | Animals Cell Differentiation Cell Lineage Cell Proliferation Disease Progression Epithelial Cells / metabolism Epithelial Cells / pathology Epithelial-Mesenchymal Transition Humans Male Mice Mutation PTEN Phosphohydrolase / deficiency PTEN Phosphohydrolase / genetics PTEN Phosphohydrolase / metabolism* Prostatic Neoplasms / genetics Prostatic Neoplasms / metabolism* Prostatic Neoplasms / pathology Signal Transduction Transcription Factors / genetics Transcription Factors / metabolism beta Catenin / metabolism* |
| IF | 6.021 |
| 引用数 | 10 |
| WOS 分野 | PATHOLOGY 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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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| 実験動物マウス | RBRC02228 |