Overexpression of PDZK1 within the 1q12-q22 amplicon is likely to be associated with drug resistance phenotype in multiple myeloma
Overexpression of PDZK1 within the 1q12-q22 amplicon is likely to be associated with drug resistance phenotype in multiple myeloma
复制标题
DOI：
10.1016/s0002-9440(10)63276-2
复制
发表时间：
2004-07-01
影响因子：
6
通讯作者：
Inazawa, J
中科院分区：
文献类型：
--
作者：
Inoue, J;Otsuki, T;Inazawa, J
我们利用比较基因组杂交技术研究了37株来自多发性骨髓瘤（mm）的细胞系的DNA拷贝数畸变，其中11株（29.7%）在1q12-q22处显示出高水平的基因扩增。使用寡核苷酸阵列进行相应的转录定位，在扩增的最小重叠区域内提取了三个上调基因（IRTA2， PDZK1和S100A6）。其中PDZK1在MM细胞系中扩增并随之过表达。在原发性MM病例中也观察到PDZK1的扩增。与未扩增PDZK1的MM细胞株相比，扩增PDZK1的MM细胞株对melphalan、顺式铂和长春新素诱导的细胞死亡表现出抗性。此外，用反义寡核苷酸下调PDZK1使细胞系KMS-11对melphalan、顺式铂和长春新素敏感。综上所述，我们的研究结果表明PDZK1可能是MM中1q12-q22扩增的靶标之一，并且可能与该类型肿瘤的恶性表型（包括耐药性）相关。
We investigated DNA copy number aberrations in 37 cell lines derived from multiple myelomas (MMs) using comparative genomic hybridization, and 11 (29.7%) showed high-level gain indicative of gene amplification at 1q12-q22. A corresponding transcriptional mapping using oligonucleotide arrays extracted three up-regulated genes (IRTA2, PDZK1, and S100A6) within the smallest region of overlapping in amplifications. Among them PDZK1 showed amplification and consequent overexpression in the MM cell lines. Amplification of PDZK1 was observed in primary cases of MM as well. MM cell lines with amplification of PDZK1 exhibited the resistance to melphalan-, cis-platin-, and vincristin-induced cell death compared with MM cell lines without its amplifications. Furthermore, down-regulation of PDZK1 with an anti-sense oligonucleotide sensitized a cell line KMS-11 to melphalan, cis-platin, and vincristin. Taken together, our results indicate that PDZK1 is likely to be one of targets for 1q12-q22 amplification in MM and may be associated with the malignant phenotype, including drug resistance, in this type of tumor.