Department of Biomedical Science, College of Life Science, CHA University, Seongnam 463-712, Korea.
Korean J Physiol Pharmacol. 2012 Aug;16(4):265-71. doi: 10.4196/kjpp.2012.16.4.265. Epub 2012 Aug 10.
HoxB4, a homeodomain-containing transcription factor, is involved in the expansion of hematopoietic stem cells and progenitor cells in vivo and in vitro, and plays a key role in regulating the balance between hematopoietic stem cell renewal and cell differentiation. However, the biological activity of HoxB4 in other cells has not been reported. In this study, we investigated the effect of overexpressed HoxB4 on cell survival under various conditions that induce death, using the Ba/F3 cell line. Analysis of phenotypical characteristics showed that HoxB4 overexpression in Ba/F3 cells reduced cell size, death, and proliferation rate. Moreover, the progression from early to late apoptotic stages was inhibited in Ba/F3 cells subjected to HoxB4 overexpression under removal of interleukin-3-mediated signal, leading to the induction of cell cycle arrest at the G2/M phase and attenuated cell death by Fas protein stimulation in vitro. Furthermore, apoptotic cell death induced by doxorubicin-treated G2/M phase cell-cycle arrest also decreased with HoxB4 overexpression in Ba/F3 cells. From these data, we suggest that HoxB4 may play an important role in the regulation of pro-B cell survival under various apoptotic death environments.
HoxB4 是一种含有同源域的转录因子，它参与体内和体外造血干细胞和祖细胞的扩增，并在调节造血干细胞更新和细胞分化之间的平衡方面发挥关键作用。然而，HoxB4 在其他细胞中的生物学活性尚未被报道。在这项研究中，我们使用 Ba/F3 细胞系研究了过表达 HoxB4 对诱导死亡的各种条件下细胞存活的影响。表型特征分析表明，HoxB4 在 Ba/F3 细胞中的过表达降低了细胞大小、死亡率和增殖率。此外，在去除白细胞介素-3 介导的信号的情况下，过表达 HoxB4 的 Ba/F3 细胞中，从早期到晚期凋亡阶段的进展被抑制，导致细胞周期在 G2/M 期停滞，并在体外通过 Fas 蛋白刺激减弱细胞死亡。此外，用阿霉素处理 G2/M 期细胞周期停滞诱导的凋亡细胞死亡也随着 Ba/F3 细胞中 HoxB4 的过表达而减少。从这些数据中，我们认为 HoxB4 可能在各种凋亡死亡环境下调节前 B 细胞的存活中发挥重要作用。
