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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 multifunctional cytokine involved in many aspects of cell growth, differentiation, aging, apoptosis, wound healing and embryonic development. As a tumor suppressor signal, TGF-β has a reduced or abnormal expression in solid tumors, and it also plays a regulatory role in normal and abnormal hematopoiesis. TGF-β inhibits cell growth throughout the normal process of hematopoiesis, cells can be stabilized in the quiescent, is a cell cycle inhibitor, down-regulation of hematopoietic and tumor protein expression. In abnormal hematopoiesis, mutations in TGF-β / Smads signaling pathway components inactivation or down-regulation of TGF-β lead to the destruction of TGF-β / Smads signal transduction pathway and abnormal growth and differentiation of tumor cells. PML-RARα suppresses TGF-β signaling and its function in acute promyelocytic leukemia through inhibition of nPML and cPML pathways. When all-trans retinoic acid treatment of PML-RARα expression decreased, TGF-β signal transduction can be restored.