维甲酸
细胞周期蛋白D
周期素D2抗原
细胞周期蛋白B
细胞周期蛋白
癌症研究
急性早幼粒细胞白血病
周期素
细胞周期蛋白D1
细胞凋亡
细胞周期蛋白A2
维甲酸
维甲酸诱导孤儿G蛋白偶联受体
细胞周期蛋白D3
生物
细胞周期蛋白B1
细胞周期蛋白
维甲酸受体
细胞生物学
分子生物学
细胞周期
生物化学
细胞周期蛋白依赖激酶1
基因
作者
Jenny Ekberg,Cecilia Brunhoff,Marcus Järås,Xiaolong Fan,Göran Landberg,Jenny L. Persson
标识
DOI:10.1016/j.biocel.2006.01.011
摘要
Deregulated cell growth and inhibition of apoptosis are hallmarks of cancer. All-trans retinoic acid induces clinical remission in patients with acute promyelocytic leukemia by inhibiting cell growth and inducing differentiation and apoptosis of the leukemic blasts. An important role of the cell cycle regulatory protein, cyclin A1, in the development of acute myeloid leukemia has previously been demonstrated in a transgenic mouse model. We have recently shown that there was a direct interaction between cyclin A1 and a major all-trans retinoic acid receptor, RAR alpha, following all-trans retinoic acid treatment of leukemic cells. In the present study, we investigated whether cyclin A1 might be involved in all-trans retinoic acid-induced apoptosis in U-937 leukemic cells. We found that all-trans retinoic acid-induced apoptosis was associated with concomitant increase in cyclin A1 expression. However, there was no induction of cyclin A1 mRNA expression following the all-trans retinoic acid-induced apoptosis. Treatment of cells with a caspase inhibitor was not able to prevent all-trans retinoic acid-induced up-regulation of cyclin A1 expression. Interestingly, induced cyclin A1 expression in U-937 cells led to a significant increase in the proportion of apoptotic cells. Further, U-937 cells overexpressing cyclin A1 appeared to be more sensitive to all-trans retinoic acid-induced apoptosis indicating the ability of cyclin A1 to mediate all-trans retinoic acid-induced apoptosis. Induced cyclin E expression was not able to initiate cell death in U-937 cells. Our results indicate that cyclin A1 might have a role in apoptosis by mediating all-trans retinoic acid-induced apoptosis.
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