Identification of intracellular factors involved with apoptosis induction by TGF-β family

TGF-β超家族成员参与多种生命现象的调节，包括初始发育、器官形成和肿瘤形成。我们发现激活素A和BMP-2抑制了B细胞杂交瘤HS-72的细胞生长，并研究了其细胞内转导机制。本研究以HS-72细胞、LS-1细胞和LS-12细胞为研究对象，通过流式细胞术分析激活素A对不同细胞的敏感性差异，发现激活素A在5-50 ng/ml浓度范围内可诱导HS-72细胞的细胞毒作用，并诱导细胞周期发生G1期阻滞和凋亡。结果表明，维甲酸对HS-72细胞毒性较小，细胞周期阻滞于G1期，而维甲酸与激活素A共刺激则能有效地诱导细胞周期阻滞于G1期，诱导细胞凋亡。激活素A和维甲酸对LS-1细胞无明显影响，但二者联合作用可使LS-1细胞发生G1期阻滞，亚G1期细胞比例增加。LS-12对活化素A和/或视黄酸呈中间型，提示活化素A和视黄酸之间的交联在诱导B系细胞凋亡中起重要作用。

Members of TGF-β superfamily are implicated in regulation of various life phenomenons, including initial development, organ formations and tumor formation. We found that activin A and BMP-2 inhibited cell growth of B cell hybridoma, HS-72 and examined its intracellular transduction mechanism. In the present study, we used three kinds of cells (HS-72 cells, LS-1 cells, and LS-12 cells) and investigated difference of sensitivity for activin A to these cells by flow cytometric analysis.We reported that activin A induced cytotoxic effects to HS-72, and induced G1 arrest in cell cycle and apoptosis at the concentration of 5-50 ng/ml. We clearly that retinoic acid induced a littel cytotoxity to HS-72 and G1 arrest in cell cycle, and that co-stimulation of retinoic acid and activin A potently induced G1 arrest and apoptosis. Activin A or retinoic acid have no effect to LS-1, however, co-stiluration of these factors induced G1 arrest and inclease of sub G1 rate of LS-1 cells. LS-12 showed intermediate type to Activin A and/or retinoic acid.Taken together, the results obtained in this study suggest that cross-talks between activin A and retinoic acid play an important role of the inductin of apoptosis in B lineage cells.