IAP family protein expression correlates with poor outcome of multiple myeloma patients in association with chemotherapy-induced overexpression of multidrug resistance genes
IAP family protein expression correlates with poor outcome of multiple myeloma patients in association with chemotherapy-induced overexpression of multidrug resistance genes
复制标题
DOI：
10.1002/ajh.20656
复制
发表时间：
2006-11-01
影响因子：
12.8
通讯作者：
Kitagawa, Masanobu
中科院分区：
文献类型：
--
作者：
Nakagawa, Yasunori;Abe, Shinya;Kitagawa, Masanobu
化疗失败的多药耐药（MDR）多发性骨髓瘤（MM）患者经常表达MDR 1蛋白，其作为保护肿瘤细胞的外排泵。介导细胞间和核质转运的肺耐药蛋白（LRP）的表达也与MM患者的化疗耐药性和较短的生存期相关。在此，我们采用定量RT-PCR技术研究了化疗诱导的MM患者MDR表达的变化。MM患者MDR 1和LRP的总体表达水平显著高于对照组，化疗后表达水平升高。化疗后半数以上患者MDR 1（14/26）或LRP（17/26）表达增加。同时检测凋亡抑制蛋白（IAP）的表达与患者预后的关系。在化疗后MDR 1表达增加的患者中，与预后良好的患者相比，预后不良的患者化疗后生存素、cIAP 1、cIAP 2和XIAP表达显著增加。同样，在LRP表达增加组中，与生存期较长的患者相比，预后不良的患者cIAP 1和cIAP 2表达显著增加。在化疗后MDR 1或LRP表达降低的患者中，化疗诱导的IAP表达变化与其预后无关。这些发现表明IAP家族蛋白可能在MM患者预后恶化中发挥作用，与化疗诱导的MDR 1或LRP过表达相关。
Multidrug-resistant (MDR) multiple myeloma (MM) patients who fail chemotherapy frequently express MDR1 protein, which serves as an efflux pump that protects neoplastic cells. The expression of lung resistance protein (LRP), which mediates intercellular and nucleocytoplasmic transport, is also correlated with chemotherapy resistance and shorter survival of MM patients. Here, we investigated the chemotherapy-induced change of MDR expression in MM patients using quantitative RT-PCR. Overall expression levels of MDR1 and LRP in MM patients were significantly higher than those in control subjects and increased after chemotherapy. More than half of the patients exhibited increased expression of MDR1 (14/26) or LRP (17/26) after chemotherapy. Also, the expression of inhibitor of apoptosis proteins (IAP) was determined in association with the prognosis of the patients. Among patients with increased MDR1-expression after chemotherapy, those with a poor outcome exhibited significant increases in survivin, cIAP1, cIAP2, and XIAP expression by chemotherapy compared with those with a good prognosis. Similarly, in the LRP expression-increased group, patients with a poor outcome showed significant increases of cIAP1 and cIAP2 expression compared with those with longer survival. In patients with reduced-MDR1 or LRP expression after chemotherapy, changes in the expression of IAPs induced by chemotherapy did not correlate with their prognosis. These findings indicate that IAP family proteins might play a role in worsening the prognosis of MM patients in association with chemotherapy-induced overexpression of MDR1 or LRP.