PTEN基因及其相关因子HIF1α在急性髓性白血病骨髓基质细胞中的表达及意义.docVIP

PTEN基因及其相关因子HIF-la在急性髓性白血病骨髓基质细胞中的表达及意义 武寿荣(江苏省滨海县人民医院江苏滨海224500) 屮图分类号】R733.3 】A 】1672-5085 (2012) 16-0010-02 】A的探讨PTEN棊因及其相关因子HIF-lalpha;在急性髓性白血病(AML) 骨髓基质细胞屮的表达及意义。方法取30例急性髓性白血病患者(AML组) 和30例非AML患者(对照组)骨髓基质细胞分离纯化后培养，以RT-PCR检测 其屮PTENmRNA的表达，并通过凝胶图像分析系统分析其相对含量。同时以 Western免疫印迹技术检测骨髓基质细胞屮PTEN和HIF-lalpha;蛋白表达。结 果急性髓性白血病患者骨髓基质细胞屮PTEN基因和蛋白的表达率及相对含量 均显著低于对照组(Plt;0.01, Plt;0.05), HIF-lalpha;蛋0表达率及表达水平显 著高于对照组(Plt;0.01, Plt;0.05)。HIF-lalpha;在骨髓基质细胞中的表达上调 与PTEN的低表达相关联(Plt;0.05)。结论PTEN基因可能是抑制白血病异常骨 髓造血形成的重要因子，而PTEN表达缺失或下调可能诱导其下游因子 HIF-lalpha;的高表达。 关键词】急性髓性白血病PTEN缺氧诱导因子-lalpha;骨髓基质细胞 Abstract】 Objective To investigate the relationship among expression of PTEN gene and HIF-lalpha; in patients with acute myeloid leukemia(AML). Methods Bone marrow stromal cells (BMSCs) from 30 AML patients and 30 non-AML controls were cultivated. The expression of PTEN mRNA were detected by RT-PCR and the relative amounts were analyzed with gel scan system. Simultaneously, the expression of PTEN and HIF-lalpha; proteins in BMSCs were measured by Western blotting. Results The expression rate and levels of PTEN mRNA and protein in AML group were all lower than that in control group(Plt;0.01，Plt;0.05). By contraries, the positive expression rate of HIF-lalpha; protein in AML group was higher than that in controls obviously(Plt;0.01,Plt;0.05) and the expression levels were significant stronger(Plt;0.05). There were certain negative correlation between PTEN and HIF-lalpha; in all BMSCs. Conclusions PTEN gene would inhibited the formation of the abnormal hematopoietic microenviroment. The loss or down-regulation of PTEN gene would lead the over-expression of HIF-lalpha; in AML. Keywords】 AML PTEN HIF-lalpha; Bone marrow stromal cell PTEN基因又名MMAC1或TEP1基因，是一种0前公认的肿瘤抑制基因， 与恶性肿瘤的生长、细胞分化、增殖、凋亡等许多病理过程密切相关［1】。研究 表明，PTEN基因对造血干细胞的活化和分化起重要的调控作用，对白血病的发 生有重要的抑制作用［2］。而PTEN基因的缺失或突变可以影响下游诸多肿瘤相关 因子的表达，其中包括缺氧诱导因子-lalpha; (HIF-lalpha;)。HIF-lalpha;是 广泛存在于人体内的一种转录因子，苏在肿瘤基质和肿瘤缺氧微环境的形成中发 挥重要的作用，对恶性肿瘤的生长、转移等皆奋影响［3］。