論文 - 詳細
| RRC ID | 43873 |
|---|---|
| 著者 | Morancho B, Parra-Palau JL, Ibrahim YH, Bernadó Morales C, Peg V, Bech-Serra JJ, Pandiella A, Canals F, Baselga J, Rubio I, Arribas J. |
| タイトル | A dominant-negative N-terminal fragment of HER2 frequently expressed in breast cancers. |
| ジャーナル | Oncogene |
| Abstract |
The transmembrane tyrosine kinase HER2 (ErbB2, neu) is a prototypical biomarker for breast cancers and a therapeutic target. Although anti-HER2 therapies are remarkably effective, HER2-positive tumors are heterogeneous and some subtypes do not respond or develop resistance to these therapies. Here we show that H2NTF, a novel N-terminal fragment of HER2, is expressed at variable levels in 60% of the breast cancer samples analyzed. Characterization of H2NTF shows that it is devoid of the tyrosine kinase domain but it readily interacts with full-length HER2 and other HER receptors. As a consequence, H2NTF acts as a dominant-negative, attenuating the signaling triggered by full-length HER receptors. Expression of H2NTF results in resistance to the treatment with low concentrations of trastuzumab in vitro. However, cells expressing H2NTF and non-expressing cells have similar sensitivity to trastuzumab in vivo, indicating that H2NTF/trastuzumab complexes trigger antibody-dependent cell-mediated cytotoxicity. |
| 巻・号 | 32(11) |
| ページ | 1452-9 |
| 公開日 | 2013-3-14 |
| DOI | 10.1038/onc.2012.152 |
| PII | onc2012152 |
| PMID | 22641219 |
| MeSH | Amino Acid Sequence Animals Breast Neoplasms / epidemiology Breast Neoplasms / genetics* Carcinoma / epidemiology Carcinoma / genetics* Female Gene Expression Regulation, Neoplastic Gene Frequency Genes, Dominant HEK293 Cells Humans Mice Mice, Inbred BALB C Mice, Inbred NOD Mice, Nude Mice, SCID Models, Biological Molecular Sequence Data Protein Isoforms / chemistry Protein Isoforms / genetics Protein Structure, Tertiary / genetics Protein Structure, Tertiary / physiology Receptor, ErbB-2 / chemistry* Receptor, ErbB-2 / genetics* Receptor, ErbB-2 / metabolism Tumor Cells, Cultured |
| IF | 7.971 |
| 引用数 | 5 |
| 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 | X(Twitter) |
| 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 | MKN7(RCB0999) |