Buske C, Becker D, Feuring-Buske M, Hannig H, Griesinger F, Hiddemann W, Wörmann B
Department of Hematology and Oncology, University of Göttingen, Germany.
Exp Hematol. 1998 Nov;26(12):1155-61.
Transforming growth factor beta (TGF-beta) is a highly conserved peptide with growth-inhibitory activity in multiple normal and transformed cell types. Signal transduction is mediated through the receptor complex, consisting of two active seronine or threonine kinases (TGF-beta-receptor I and II) and the receptor-associated proteins betaglycan (TGF-beta-receptor III) and endoglin. In this study, we assessed the analysis of the role of TGF-beta and the transcription of the genes for TGF-beta and its receptor in highly purified leukemic B-cell precursors (BCPs) of patients with common acute lymphoblastic leukemia (cALL). Leukemic BCPs were positive for gene transcription of TGF-beta (9/9), the TGF-beta-receptor I (9/9), the TGF-beta-receptor II (6/6), betaglycan (5/6), and endoglin (6/6). Incubation with TGF-beta significantly reduced the cell viability of leukemic BCPs by a mean of 45% (p = 0.0009). The reduction of cell viability was associated with the induction of apoptosis by a mean of 31%. TGF-beta caused significant suppression of the S phase (p = 0.002) and accumulation in the G0/G1 phase (p = 0.0005). It also reduced expression of the adhesion surface receptor CD18 and the Fas antigen CD95 from 58% to 40% and from 48% to 27%, respectively. The data indicate that TGF-beta is a negative growth signal in leukemic BCPs and point to an additional role of TGF-beta as an immunomodulatory cytokine, suggesting a complex role of TGF-beta in the leukemogenesis of cALL.
转化生长因子β（TGF-β）是一种高度保守的肽，在多种正常和转化细胞类型中具有生长抑制活性。信号转导通过受体复合物介导，该复合物由两种活性丝氨酸或苏氨酸激酶（TGF-β受体I和II）以及受体相关蛋白β聚糖（TGF-β受体III）和内皮糖蛋白组成。在本研究中，我们评估了TGF-β的作用分析以及TGF-β及其受体基因在常见急性淋巴细胞白血病（cALL）患者高度纯化的白血病B细胞前体（BCP）中的转录情况。白血病BCP的TGF-β（9/9）、TGF-β受体I（9/9）、TGF-β受体II（6/6）、β聚糖（5/6）和内皮糖蛋白（6/6）基因转录呈阳性。用TGF-β孵育可使白血病BCP的细胞活力平均显著降低45%（p = 0.0009）。细胞活力的降低与平均31%的凋亡诱导相关。TGF-β导致S期显著抑制（p = 0.002）并在G0/G1期积累（p = 0.0005）。它还使黏附表面受体CD18和Fas抗原CD95的表达分别从58%降至40%和从48%降至27%。数据表明TGF-β是白血病BCP中的负性生长信号，并指出TGF-β作为免疫调节细胞因子的额外作用，提示TGF-β在cALL白血病发生中具有复杂作用。
