E—cadherin在白血病细胞膜表面的表达及与β-catenin细胞膜定位的关系

Leukemia cell surface expression of E-cadherin and its correlation with membrane localization of β- catenin

目的研究E-cadherin在白血病细胞膜表面的表达并确定与其下游信号分子β-catenin细胞膜定位的关系。方法通过免疫荧光标记、激光共聚焦显微镜观察46例白血病患者和17名正常人骨髓细胞膜表面E-cadherin的表达，并分析其与β-catenin在细胞内分布的相关性。结果白血病患者E-cadherin表达水平（中位平均荧光强度16．78）显著低于正常人（26．03）；进一步随机选取14份标本测定细胞膜表面E—cadherin的表达及β—catenin的细胞膜分布并分析二者的相关性，结果显示E—cadherin的表达与β-catenin的细胞膜分布明显相关（r=0．74，P=0．002）；5-氮杂脱氧胞苷（5-Aza—CdR）诱导白血病细胞中E—cadherin表达后，β—catenin在细胞膜的分布增加，而细胞核内的β—catenin定位减少，初步证实E-cadherin表达后可募集β-catenin到细胞膜。结论白血病细胞中E—cadherin表达降低或缺失可引起β＇-catenin从细胞膜释放并进入细胞核，最终可能会引起β—catenin靶基因的转录。

Objective To investigate the expression of cell surface E-cadherin in leukemia cell and the correlation of cell membrane localization of β-catenin with E-cadherin expression. Methods Bone marrow samples from 46 patients with acute leukemia and 17 normal donors were analyzed. Cell surface expression of E-cadherin and membrane localization of β-catenin were labeled by immunofluorescence and analyzed with a laser scanning confocal fluorescence microscope in 14 specimens. Results Cell surface E-cadherin expression level was significantly lower in leukemia cells （with the median fluorescent intensity of 16.78） than in normal hematopoietic progenitors （26, 03 ）. Correlation analysis showed that cell membrane localization of β-catenin was correlated with E-cadherin expression（ r =0. 74, P = 0.002）. After E-cadherin was induced to express in leukemic cell by 5-Aza-CdR, membranous expression of β-catenin was elevated while the nuclear expression reduced, indicating that E-cadherin-mediated adhesions could recruit β-catenin to cell membrane. Conclusion The loss of E-cadherin in leukemia cells may result in β-catenin translocating to the nuclear and transcriptional activation of its target genes.