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Expression of activated c-erbB-2 oncogene induces sensitivity to cisplatin in human gallbladder adenocarcinoma cells
V Boudny1, Y Murakami, S Nakano
1First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Abstract:
Overexpression of the c-erbB-2/HER-2/neu protooncogene which encodes for the tyrosine kinase receptor p185neu, has been observed frequently in cisplatin resistant human tumors, such as colorectal, breast, and non-small-cell lung cancers, and is known to induce resistance to cisplatin (CDDP) in vitro. To confirm a direct relationship between erbB-2 expression and CDDP resistance, we examined the role of erbB-2 in the cellular sensitivity to cisplatin using erbB-2 transfected HAG-1 human gallbladder adenocarcinoma cell lines. Three out of four cell lines, which stably expressed ErbB-2 protein (p185neu), did not show CDDP resistance but acquired sensitivity to cisplatin, compared to non-transfected cells. This chemosensitivity appears to be inversely correlated with the abundance of p185neu. Although the mechanism still remains unclear, these results suggest that sensitivity to CDDP in erbB-2 expressed cells may vary, depending on the cell type.
Insights
Overexpression of the c-erbB-2/HER-2/neu protooncogene is linked to cisplatin resistance. However, this study found that erbB-2 expression in gallbladder cancer cells increased sensitivity to cisplatin, suggesting cell-type specific effects.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The c-erbB-2/HER-2/neu protooncogene encodes the p185neu tyrosine kinase receptor.
- Overexpression of HER-2/neu is frequently observed in cisplatin-resistant human tumors like colorectal, breast, and lung cancers.
- HER-2/neu overexpression is known to induce in vitro resistance to cisplatin (CDDP).
Purpose of the Study:
- To investigate the direct relationship between erbB-2 expression and cellular sensitivity to cisplatin.
- To examine the role of erbB-2 in mediating cisplatin resistance or sensitivity in human cancer cells.
Main Methods:
- Utilized erbB-2 transfected HAG-1 human gallbladder adenocarcinoma cell lines.
- Compared cisplatin sensitivity between cell lines with stable erbB-2 expression and non-transfected control cells.
- Assessed the correlation between p185neu protein abundance and chemosensitivity.
Main Results:
- Three out of four erbB-2 expressing cell lines acquired sensitivity to cisplatin, contrary to expectations.
- Acquired chemosensitivity to cisplatin was inversely correlated with the abundance of p185neu protein.
- Non-transfected cells did not exhibit the same sensitivity profile as erbB-2 expressing cells.
Conclusions:
- The results suggest an inverse correlation between erbB-2 expression and cisplatin sensitivity in HAG-1 gallbladder cancer cells.
- The mechanism underlying this observed chemosensitivity remains unclear.
- Sensitivity to cisplatin in erbB-2 expressing cells may be cell-type dependent, challenging previous assumptions.