Proteome alterations in human hepatoma cells transfected with antisense epidermal growth factor receptor sequence
1Research Center for Proteome, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, PR China.
Abstract:
The epidermal growth factor (EGF) is a member of the growth factor superfamily that can stimulate the proliferation of many types of cells. Overexpression of EGF receptor (EGFR) was observed in many types of cancer cells. Anti-EGFR antibodies or antisense nucleic acid sequences of EGFR can suppress the growth of hepatoma cells. In order to further investigate the proteome alterations associated with malignant growth of the human hepatoma cells and the influence of EGFR signal pathway on the cellular proteome, we have comparatively analyzed the proteomes of human hepatoma cells transfected with antisense EGFR sequence (cell strain JX-1) and its control cells (cell strain JX-0) by two-dimensional (2-D) gel electrophoresis and mass spectrometry. Image analysis of silver-stained 2-D gels revealed that 40 protein spots showed significant expression changes in JX-1 cells compared to JX-0 cells. Three of them, including the tumor suppressor protein maspin, changed with tendency to the normal levels. Two protein spots were identified as HSP27 in the same gel, and one of them had a reduced level in JX-1 cells. The apparent alterations of HSP27 in expression level might be the results from their differential chemical modifications, suggesting the effect of dynamic post-translational modifications of proteins on the growth of hepatoma cells. Other proteins such as glutathione peroxidase (GPX-1) and 14-3-3-sigma also exhibited altered expression in JX-1 cells, and their functional implications are discussed.
Insights
Investigating human hepatoma cells, this study analyzed proteome changes after reducing the epidermal growth factor receptor (EGFR) pathway. Key proteins like maspin and HSP27 showed altered expression, offering insights into cancer growth.
Area of Science:
- Proteomics
- Cancer Biology
- Molecular Oncology
Background:
- Epidermal growth factor (EGF) stimulates cell proliferation.
- Overexpression of the EGF receptor (EGFR) is common in cancers.
- Targeting EGFR can suppress hepatoma cell growth.
Purpose of the Study:
- To investigate proteome alterations in human hepatoma cells with reduced EGFR signaling.
- To understand the influence of the EGFR pathway on cellular proteome dynamics.
Main Methods:
- Comparative proteomic analysis using two-dimensional (2-D) gel electrophoresis.
- Mass spectrometry for protein identification.
- Analysis of human hepatoma cell strains JX-1 (antisense EGFR) and JX-0 (control).
Main Results:
- 40 protein spots exhibited significant expression changes in JX-1 cells compared to JX-0.
- Tumor suppressor maspin levels tended toward normal in JX-1 cells.
- Altered expression of heat shock protein 27 (HSP27), glutathione peroxidase (GPX-1), and 14-3-3-sigma was observed.
Conclusions:
- EGFR signaling significantly impacts the hepatoma cell proteome.
- Dynamic post-translational modifications may influence hepatoma cell growth.
- Altered protein expression provides potential targets for therapeutic intervention.
