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

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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.