TGF-β/Smads信号转导与白血病细胞的关系  

Relationship between TGF-β/Smads signal transduction and leukemic cells

作　　者：沈璟璟[1] 钟璐[1] 陈芳源[1] 

机构地区：[1]上海交通大学医学院仁济医院血液科,上海200001

出　　处：《上海交通大学学报（医学版）》2008年第8期1038-1041,共4页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市科委基金(04ZR14106)~~

摘　　要：转化生长因子β(TGF-β)是一种多功能的细胞因子,参与细胞的生长、分化、衰老、凋亡、伤口愈合、胚胎发育等多方面的调节。TGF-β作为一种肿瘤抑制信号,在实体肿瘤中有信号降低或异常表达,在正常、异常造血中也有调节作用。TGF-β抑制细胞生长的作用贯穿于整个正常造血过程,能将细胞稳定在静止期,是细胞周期抑制物,下调造血刺激因子及肿瘤蛋白的表达。在异常造血过程中,TGF-β/Smads信号通路组成部分的突变失活或TGF-β表达下调导致TGF-β/Smads信号转导通路破坏,肿瘤细胞得以异常生长和分化。PML-RARα能通过抑制nPML和cPML途径来抑制急性早幼粒细胞白血病的TGF-β信号转导及其功能。当全反式维甲酸治疗PML-RARα表达降低后,TGF-β信号转导又可恢复。Transforming growth factor-β（TGF-β） is a kind of multifunctional cytokine that regulates cell growth,differentiation,cellular senescence,apoptosis,wound healing and embryo development.As a tumor suppressor,deregulated or aberrant TGF-β signaling has been strongly implicated in human solid tumors,as well as in normal and malignant hematopoiesis.TGFβ exerts an inhibitory role during the whole procedure of hematopoiesis.As a cell cycle inhibitor,it maintains cells in a quiescent state and can downregulate expression of hematopoiesis activators and oncoproteins.In malignant hematopoiesis,altered expression of coactivators or corepressors involve in TGF-β-induced transcriptional responses and loss/disruption of TGF-β target gene expression.Then malignant cells grow and differentiate abnormally.In acute promyelocytic leukemia,PML-RARα may inhibit TGF-β signaling through inhibition of cPML and nPML.Degradation of PML-RARα by ATRA restores this signaling pathway.

关 键 词：转化生长因子-Β SMADS蛋白 白血病 

分 类 号：R733.7[医药卫生—肿瘤] Q257[医药卫生—临床医学]