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.
Boudny
V
V
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Murakami
Y
Y
Nakano
S
S
Niho
Y
Y
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015870:Gene Expression; D018734:Genes, erbB-2; D006801:Humans; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D002945:Cisplatin