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Determining Optimal Cytotoxic Activity of Human Her2neu Specific CD8 T cells by Comparing the Cr51 Release Assay to the xCELLigence System
Published on: August 8, 2012
The tumor suppressor RECK interferes with HER-2/Neu dimerization and attenuates its oncogenic signaling
Kun-Jing Hong1, Ming-Chuan Hsu, Ming-Fen Hou
1Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
Abstract:
Our previous study demonstrates that HER-2/Neu oncogene inhibits a matrix metalloproteinase inhibitor and tumor metastasis suppressor RECK to promote metastasis. Conversely, the effect of RECK on the oncogenic function of HER-2/Neu is unknown. Ectopic expression of RECK in 293T cells and HER-2/Neu-overexpressing breast cancer cells shows that RECK and HER-2/Neu are co-localized and these two proteins can be co-immunoprecipitated. RECK inhibits HER-2/Neu receptor dimerization and autophosphorylation, which causes reduction of ERK and AKT kinase activity and down-regulation of HER-2/Neu target genes. RECK expression is reduced in 58.8% of breast cancer tissues and is associated with lymph node invasion supporting its anti-metastatic role. Collectively, we provide the first evidence that RECK can negatively regulate oncogenic activity of HER-2/Neu by inhibiting receptor dimerization.
Insights
Reversion-inducing cysteine-rich protein withkazal motifs (RECK) suppresses breast cancer metastasis by inhibiting the HER-2/Neu oncogene. RECK blocks HER-2/Neu receptor dimerization, reducing cancer cell growth and spread.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The HER-2/Neu oncogene promotes tumor metastasis.
- The role of RECK (Reversion-inducing cysteine-rich protein with kazal motifs) in HER-2/Neu oncogenic function was previously unknown.
- RECK acts as a tumor metastasis suppressor.
Purpose of the Study:
- To investigate the effect of RECK on the oncogenic function of HER-2/Neu.
- To elucidate the molecular mechanisms by which RECK regulates HER-2/Neu signaling.
- To determine the clinical relevance of RECK expression in breast cancer.
Main Methods:
- Ectopic expression of RECK in 293T cells and HER-2/Neu-overexpressing breast cancer cells.
- Co-localization and co-immunoprecipitation assays to study protein interactions.
- Assessment of HER-2/Neu receptor dimerization and autophosphorylation.
- Analysis of downstream signaling pathways (ERK, AKT) and target gene expression.
- Evaluation of RECK expression in human breast cancer tissues and correlation with lymph node invasion.
Main Results:
- RECK and HER-2/Neu were found to co-localize and interact.
- RECK inhibited HER-2/Neu receptor dimerization and autophosphorylation.
- This inhibition led to reduced ERK and AKT kinase activity.
- Down-regulation of HER-2/Neu target genes was observed.
- Reduced RECK expression was detected in 58.8% of breast cancer tissues and correlated with lymph node invasion.
Conclusions:
- RECK negatively regulates the oncogenic activity of HER-2/Neu.
- RECK inhibits HER-2/Neu signaling by preventing receptor dimerization.
- RECK functions as an anti-metastatic factor in breast cancer, and its reduced expression is clinically significant.
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