Overexpressed max is not oncogenic and attenuates myc-induced lymphoproliferation and lymphomagenesis in transgenic mice.
Overexpressed max is not oncogenic and attenuates myc-induced lymphoproliferation and lymphomagenesis in transgenic mice.
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发表时间：
1995-03
期刊：
影响因子：
8
通讯作者：
G. Lindeman;A. W. Harris;M. Bath;R. Eisenman;Jerry M. Adams
中科院分区：
文献类型：
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作者：
G. Lindeman;A. W. Harris;M. Bath;R. Eisenman;Jerry M. Adams
Myc癌蛋白的细胞生长促进功能需要其与Max蛋白的异源二聚化，但Max也可以形成抑制Myc作用的复合物。为了确定体内max过表达是否是致癌的，以及它是否可以调节Myc的作用，我们产生了转基因小鼠，其中max基因通过连接的免疫球蛋白重链增强子（E mu）在淋巴细胞中定向表达。在实质上高于内源性最大基因的水平的转基因的表达并没有扰乱成年动物的淋巴稳态，也不容易发生淋巴瘤。非常年幼的动物中B淋巴细胞的数量减少。此外，双转基因E mu-myc/E mu-max小鼠的分析显示，max过表达减弱了由E mu-myc转基因诱导的癌前B淋巴细胞增殖状态，并降低了淋巴瘤发病率。这些结果表明，体内Max表达的升高抑制了Myc的功能。
The cellular growth promoting function of the Myc oncoprotein requires its heterodimerization with the Max protein, but Max can also form complexes that inhibit Myc action. To determine whether max overexpression in vivo is oncogenic and whether it can modulate the action of Myc, we generated transgenic mice in which the max gene was directed to express in lymphoid cells by a linked immunoglobulin heavy chain enhancer (E mu). Expression of the transgene at substantially higher levels than the endogenous max gene did not perturb lymphoid homeostasis in adult animals nor predispose to lymphomagenesis. The numbers of B-lymphoid cells in very young animals were reduced. Moreover, analysis of bi-transgenic E mu-myc/E mu-max mice revealed that max overexpression attenuated the premalignant B-lymphoproliferative state induced by an E mu-myc transgene and reduced the rate of lymphoma onset. These results suggest that elevation of Max expression in vivo inhibits the function of Myc.