Development of novel anti-tumor drugs inhibiting Anamorsin and Picot binding

Anamorsin(AM)最初是作为一种抵抗细胞凋亡的分子被分离出来的。AM缺乏的小鼠在妊娠后期死亡；AM对于胚胎生长和造血是不可或缺的。此外，我们先前的研究表明，在大约30%的B细胞肿瘤病例中，AM过度表达。在这项工作中，我们重点研究了AM转基因(TG)小鼠的B细胞。与WT小鼠相比，脂多糖刺激的AM-TG-B细胞增殖能力降低。脂多糖刺激的AM-TG-B细胞ERK1/2和IKBA的磷酸化水平也降低。基于DNA微阵列结果的上游分析表明，在内毒素刺激的AM、TG和WT B细胞中，RAS活性在内毒素刺激的AM TG B细胞中显著降低。我们还通过RAS实验证实了脂多糖对AM-TG小鼠RAS活性的损伤作用。我们的发现表明AM可能通过抑制RAS的激活而在内毒素信号通路中起到负性调节的作用，这是AM的一项新功能

Anamorsin (AM) was originally isolated as a molecule that conferred resistance to apoptosis. AM deficient mice die during late gestation; AM is indispensable for embryo growth and hematopoiesis. Furthermore, our previous study showed AM overexpression in approximately 30% of B cell neoplasm cases. In this work, we focused on B cells of AM transgenic (Tg) mice. LPS-stimulated proliferation of AM Tg B cells was decreased compared with WT mice. Phosphorylation of Erk1/2 and IKBa in LPS-stimulated AM Tg B cells was also decreased. Upstream analysis based on the results of DNA micro array comparing AM Tg and WT B cells stimulated with or without LPS suggested that Ras activation was decreased in LPS-stimulated AM Tg B cells. We also confirmed impairment of LPS induced Ras activation in AM Tg mice by Ras assay. Our findings indicate the possibility that AM plays a role of negative regulation in LPS signaling pathway through the inhibition of Ras activation, which is a novel function of AM.