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Programmed cell death 4 and BCR-ABL fusion gene expression are negatively correlated in chronic myeloid leukemia

机译:程序性细胞死亡4和BCR-ABL融合基因表达在慢性粒细胞白血病中呈负相关

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摘要

Programmed cell death 4 (PDCD4) is a tumor suppressor that inhibits carcinogenesis, tumor progression and invasion by preventing gene transcription and translation. Downregulation of PDCD4 expression has been identified in multiple types of human cancer, however, to date, the function of PDCD4 in leukemia has not been investigated. In the present study, PDCD4 mRNA and protein expression was investigated in 50 patients exhibiting various phases of chronic myeloid leukemia (CML) and 20 healthy individuals by reverse transcription-quantitative polymerase chain reaction and western blot analysis. PDCD4 expression and cell proliferation was also investigated following treatment with the tyrosine kinase inhibitor, imatinib, in K562 cells. The results demonstrated that PDCD4 mRNA and protein expression was decreased in all CML samples when compared with healthy controls, who expressed high levels of PDCD4 mRNA and protein. No significant differences in PDCD4 expression were identified between chronic phase, accelerated phase and blast phase CML patients. In addition, PDCD4 expression was negatively correlated with BCR-ABL gene expression (r=−0.6716; P<0.001). Furthermore, K562 cells treated with imatinib exhibited significantly enhanced PDCD4 expression. These results indicate that downregulation of PDCD4 expression may exhibit a critical function in the progression and malignant proliferation of human CML.
机译:程序性细胞死亡4(PDCD4)是一种肿瘤抑制因子,可通过阻止基因转录和翻译来抑制癌变,肿瘤进展和侵袭。已经在多种类型的人类癌症中鉴定了PDCD4表达的下调,但是,迄今为止,尚未研究PDCD4在白血病中的功能。在本研究中,通过逆转录定量聚合酶链反应和蛋白质印迹分析,对50例表现出慢性髓性白血病(CML)不同阶段的患者和20例健康个体的PDCD4 mRNA和蛋白表达进行了研究。在酪氨酸激酶抑制剂伊马替尼治疗K562细胞后,还研究了PDCD4的表达和细胞增殖。结果表明,与健康对照相比,所有CML样品中PDCD4 mRNA和蛋白质表达均降低,健康对照者表达高水平的PDCD4 mRNA和蛋白质。在慢性期,加速期和爆炸期CML患者之间未发现PDCD4表达的显着差异。另外,PDCD4表达与BCR-ABL基因表达负相关(r = -0.6716; P <0.001)。此外,用伊马替尼处理的K562细胞表现出明显增强的PDCD4表达。这些结果表明,PDCD4表达的下调可能在人类CML的进展和恶性增殖中发挥关键作用。

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