Barnes M N, Deshane J S, Siegal G P, Alvarez R D, Curiel D T
Departments of Obstetrics and Gynecology and Pathology, Cell Biology, and Surgery, and Gene Therapy Program, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Clin Cancer Res. 1996 Jul;2(7):1089-95.
erbB-2 is a cell surface transmembrane glycoprotein which, when overexpressed, has been shown to be relevant to intrinsic tumor cell chemoresistance. Thus, strategies to down-regulate cell surface erbB-2 have resulted in enhanced tumor cell chemosensitivity. We have recently reported a gene therapy strategy to down-modulate erbB-2 expression using a plasmid construct encoding an intracellular single chain antibody. Therefore, we now demonstrate enhanced chemosensitivity to cis-diamminedichloroplatinum in erbB-2 overexpressing tumor cells and a model system of stable clones using an intracellular single chain antibody. These findings are consistent with the hypothesis that erbB-2 plays a role in tumor cell chemoresistance. In addition, these findings represent a novel gene therapy approach to overcome erbB-2-mediated tumor cell chemoresistance.
erbB-2是一种细胞表面跨膜糖蛋白，当过度表达时，已被证明与肿瘤细胞内在的化学抗性相关。因此，下调细胞表面erbB-2的策略已导致肿瘤细胞化学敏感性增强。我们最近报道了一种基因治疗策略，即使用编码细胞内单链抗体的质粒构建体来下调erbB-2的表达。因此，我们现在证明，在erbB-2过表达的肿瘤细胞和使用细胞内单链抗体的稳定克隆模型系统中，对顺二氯二氨铂的化学敏感性增强。这些发现与erbB-2在肿瘤细胞化学抗性中起作用的假设一致。此外，这些发现代表了一种克服erbB-2介导的肿瘤细胞化学抗性的新型基因治疗方法。
