Song Ju Han, Choi Cheol Hee, Yeom Hye-Jung, Hwang Seung Yong, Kim Tae Sung
College of Pharmacy and Genome Center for Hematopoietic Diseases, Chonnam National University, Gwangju, Republic of Korea.
Life Sci. 2006 Jun 6;79(2):193-202. doi: 10.1016/j.lfs.2005.12.054. Epub 2006 Feb 3.
Acquired drug-resistance phenotype is a key factor in the relapse of patients suffering hematological malignancies. In order to investigate the genes involved in drug resistance, a human leukemia cell line that is resistant to doxorubicin, an anthracycline anticancer agent (AML-2/DX100), was selected and its gene expression profile was analyzed using a cDNA microarray. A number of genes were differentially expressed in the AML-2/DX100 cells, compared with the wild type (AML-2/WT). Pro-apoptotic genes such as TNFSF7 and p21 (Cip1/Waf1) were significantly down-regulated, whereas the IKBKB, PCNA, stathmin 1, MCM5, MMP-2 and MRP1 genes, which are involved in anti-apoptotic or cell cycle progression, were over-expressed. The AML-2/DX100 cells were also resistant to other anticancer drugs, including daunorubicin and camptothecin, and the expression levels of the differentially regulated genes such as STMN1, MMP-2 and CTSG, were constantly maintained. This suggests that the deregulated genes obtained from the DNA microarray analysis in a cell line model of drug resistance might contribute to the acquired drug resistance after chronic exposure.
获得性耐药表型是血液系统恶性肿瘤患者复发的关键因素。为了研究与耐药相关的基因，我们选择了一种对蒽环类抗癌药物阿霉素耐药的人白血病细胞系（AML-2/DX100），并使用cDNA微阵列分析其基因表达谱。与野生型（AML-2/WT）相比，AML-2/DX100细胞中有许多基因差异表达。促凋亡基因如TNFSF7和p21（Cip1/Waf1）显著下调，而参与抗凋亡或细胞周期进程的IKBKB、PCNA、stathmin 1、MCM5、MMP-2和MRP1基因则过度表达。AML-2/DX100细胞对其他抗癌药物（包括柔红霉素和喜树碱）也有耐药性，并且差异调节基因如STMN1、MMP-2和CTSG的表达水平持续维持。这表明在耐药细胞系模型中通过DNA微阵列分析获得的失调基因可能导致长期暴露后的获得性耐药。
