Expression of activated c-erbB-2 oncogene induces sensitivity to cisplatin in human gallbladder adenocarcinoma cells.

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.