Boudny V, Murakami Y, Nakano S, Niho Y
First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Anticancer Res. 1999 Nov-Dec;19(6B):5203-6.
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.
编码酪氨酸激酶受体p185neu的原癌基因c-erbB-2/HER-2/neu的过表达，在顺铂耐药的人类肿瘤中经常被观察到，如结直肠癌、乳腺癌和非小细胞肺癌，并且已知在体外可诱导对顺铂（CDDP）的耐药性。为了证实erbB-2表达与CDDP耐药性之间的直接关系，我们使用erbB-2转染的HAG-1人胆囊腺癌细胞系研究了erbB-2在细胞对顺铂敏感性中的作用。与未转染的细胞相比，四个稳定表达ErbB-2蛋白（p185neu）的细胞系中有三个没有表现出CDDP耐药性，反而对顺铂获得了敏感性。这种化学敏感性似乎与p185neu的丰度呈负相关。虽然机制仍不清楚，但这些结果表明，erbB-2表达细胞对CDDP的敏感性可能因细胞类型而异。
