演題詳細

一般口演 / Oral Session

一般口演 91 (Oral Session 91) :AML:細胞の特性 2

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日程
2013年10月13日(日)
時間
16:00 - 17:00
会場
第3会場 / Room No.3 (さっぽろ芸文館 3F 蓬莱)
座長・司会
矢野 道広 (Michihiro Yano):1
1:秋田大学医学部 小児科
 
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MT-1G disturbs ATRA induced differentiation of NB4 cells through the inhibition of p53

演題番号 : OS-3-103

平子 奈緒美 (Naomi Hirako):1、中野 博子 (Hiroko Nakano):2、高橋 伸一郎 (Shinichiro Takahashi):1,2

1:Div. Mol. Hematol., Kitasato Univ. Grad. Sch. Med. Sci., Japan、2:Div. Hematol., Kitasato Univ. Sch. Allied Health Sci., Japan

 

We previously demonstrated that PU.1 directly represses Metallothionein (MT)-1A, G (MT-1s) gene promoter (Imoto et al., J. Biol. Chem., 2010). MT-1s play a role in ROS scavenging, metal chelation and cell growth but the roles in myelopoiesis are largely unknown. In the last JSH meeting, we demonstrated that over-expression of MT-1G inhibits ATRA induced NB4 cell differentiation, shown by NBT reduction assay and myeloid marker expression studies. In this study, we investigated the molecular effects by the over-expression of MT-1G in these cells. First, we performed microarray analyses and revealed the changes in expression of several myeloid differentiation-related genes (myeloperoxidase, azurocidin 1, etc.) induced by ATRA were disturbed in NB4 cells stably expressing human MT-1G (NB4MTOE cells). Since G1 arrest is a hallmark of ATRA-induced NB4 cell differentiation, we examined cell cycle profiles and revealed a decrease in G1 accumulation, as well as decreases in the induction of p53 target genes, p21WAF1/CIP1 and cyclin D1, by ATRA in NB4MTOE cells. p53 is a zinc finger transcription factor and depletion of intracellular zinc result in the loss of its DNA-binding capacity (Verhaegh et al., Mol. Carcinog., 1998). EMSA and ChIP assays revealed that the DNA-binding activity of p53 tended to be attenuated in ATRA-treated NB4MTOE cells. Consistently, NB4MTOE cells are resistant to cytarabine and daunorubicine. Taken together, overexpression of MT-1G results in the inhibition of p53 function, which may play a role in the block of ATRA induced differentiation of NB4 cells.

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