Nakayama Kentaro, Kanzaki Atsuko, Ogawa Kenji, Miyazaki Kohji, Neamati Nouri, Takebayashi Yuji
Department of Pathology Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Int J Cancer. 2002 Oct 10;101(5):488-95. doi: 10.1002/ijc.10608.
Intrinsic or acquired resistance to chemotherapy is the major obstacle to overcome in the treatment of patients with solid carcinoma. Cisplatin is one of the most effective chemotherapeutic agents for treating ovarian carcinoma. Recently, copper-transporting P-type adenosine triphosphatase (ATP7B) has been demonstrated as one of the genes responsible for cisplatin resistance in vitro. We hypothesized that the expression of ATP7B gene increases resistance to cisplatin in ovarian carcinoma and a priori knowledge of its expression is important for the choice of therapy. The aim of our study was to assess the role of ATP7B gene in ovarian carcinoma and compare its expression with those of multidrug resistance-related transporters such as MDR1, MRP1, MRP2, LRP and BCRP genes. The transporters' gene expression profiles from 82 patients treated with cisplatin-based chemotherapy after surgery were assessed by RT-PCR. We did not observe any significant correlation between ATP7B gene expression and those of MDR1, MRP1, MRP2, LRP or BCRP. The expression level of ATP7B gene was significantly increased (p < 0.05) in patients with moderately-/poorly-differentiated ovarian carcinomas treated with cisplatin-based chemotherapy, thus ATP7B may serve as an independent prognostic factor in these patients. In contrast, the expression level of MDR1, MRP1, MRP2, LRP and BCRP genes were not prognostic indicators of disease. These findings suggest that ATP7B gene may be considered as a novel chemoresistance marker and that inhibitor(s) of ATP7B might be useful, in patients with ovarian carcinoma treated with cisplatin-based chemotherapy.
内在性或获得性化疗耐药是实体癌患者治疗中需要克服的主要障碍。顺铂是治疗卵巢癌最有效的化疗药物之一。最近，铜转运P型三磷酸腺苷酶（ATP7B）已被证明是体外顺铂耐药相关基因之一。我们推测ATP7B基因的表达增加了卵巢癌对顺铂的耐药性，并且其表达的先验知识对治疗方案的选择很重要。我们研究的目的是评估ATP7B基因在卵巢癌中的作用，并将其表达与多药耐药相关转运蛋白如MDR1、MRP1、MRP2、LRP和BCRP基因的表达进行比较。通过逆转录聚合酶链反应（RT-PCR）评估了82例术后接受顺铂化疗患者的转运蛋白基因表达谱。我们未观察到ATP7B基因表达与MDR1、MRP1、MRP2、LRP或BCRP基因表达之间存在任何显著相关性。在接受顺铂化疗的中/低分化卵巢癌患者中，ATP7B基因的表达水平显著升高（p<0.05），因此ATP7B可能是这些患者的一个独立预后因素。相比之下，MDR1、MRP1、MRP2、LRP和BCRP基因的表达水平不是疾病的预后指标。这些发现表明，ATP7B基因可被视为一种新的化疗耐药标志物，并且ATP7B抑制剂可能对接受顺铂化疗的卵巢癌患者有用。
