| 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
|
| リソース情報 |
| ヒト・動物細胞 |
MKN7(RCB0999) |
