Blocking c-Myc and Max expression inhibits proliferation and induces differentiation of normal and leukemic myeloid cells.
Blocking c-Myc and Max expression inhibits proliferation and induces differentiation of normal and leukemic myeloid cells.
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发表时间：
1995-12
期刊：
影响因子：
8
通讯作者：
H. Q. Nguyen;M. Selvakumaran;D. Liebermann;B. Hoffman
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文献类型：
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作者：
H. Q. Nguyen;M. Selvakumaran;D. Liebermann;B. Hoffman
鉴于c-Myc在生长控制、分化和凋亡中发挥的核心作用，了解c-Myc的功能将增加我们对正常细胞发育的理解，以及这些过程中的改变如何导致恶性肿瘤。C-Myc是终末髓细胞分化的负调节因子；因此，确定阻断c-Myc表达对增殖和分化的影响是很有趣的。在这项工作中，我们发现在缺乏外源分化诱导剂的情况下，阻断髓母细胞白血病M1细胞中c-Myc或其分子伴侣Max的表达可激活分化程序；细胞呈中期髓样形态。此外，当c-Myc和Max的表达同时被阻断时，许多细胞发生终末分化。最后，将这些研究扩展到富含成髓细胞的正常骨髓（BM）细胞，表明阻断c-Myc或Max的表达加速了gm - csf诱导的粒细胞和单核细胞谱系的分化。因此，可以得出结论，在特定发育阶段阻断髓细胞中c-Myc或Max的表达可激活并加速终分化程序。
Given the central role c-Myc plays in growth control, differentiation and apoptosis, understanding how c-Myc functions will increase our understanding about normal cell development, and how alterations in these processes can lead to malignancy. C-Myc is a negative regulator of terminal myeloid differentiation; therefore, it was of interest to determine what effect blocking c-Myc expression would have on proliferation and differentiation. In this work we showed that blocking expression of either c-Myc or Max, its molecular partner, in myeloblastic leukemia M1 cells activated the differentiation program in the absence of an exogenous source of differentiation inducer; the cells assumed an intermediate stage myeloid morphology. Moreover, when both c-Myc and Max expression was concommitantly blocked, many of the cells underwent terminal differentiation. Finally, extending these studies to myeloblast enriched normal bone marrow (BM) cell has shown that blocking expression of either c-Myc or Max accelerated GM-CSF-induced differentiation along both the granulocytic and monocytic lineages. Thus, it can be concluded that blocking either c-Myc or Max expression in myeloid cells at specific stages of development activates and accelerates the terminal differentiation program.