c-Myc regulates mammalian body size by controlling cell number but not cell size
c-Myc regulates mammalian body size by controlling cell number but not cell size
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DOI：
10.1038/414768a
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发表时间：
2001-12-13
期刊：
影响因子：
64.8
通讯作者：
Bishop, JM
中科院分区：
文献类型：
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作者：
Trumpp, A;Refaeli, Y;Bishop, JM
原癌基因 c-myc 的过度表达与多种人类肿瘤的发生有关。 c-Myc 似乎调节多种生物过程，但其在肿瘤发生和正常生理学中的作用仍然是个谜(1)。在这里，我们报告了一系列等位基因小鼠的产生，其中 c-myc 表达逐渐降低至零。这些小鼠的成纤维细胞增殖减少，c-Myc 功能完全丧失后，它们退出细胞周期。我们发现 Myc 活性不是细胞生长所必需的，但它确实决定了重新进入细胞周期的活化 T 细胞的百分比。在体内，c-Myc 水平的降低会因多器官发育不全而导致体重减轻，而果蝇 dmyc 突变体则因营养不良而体形较小 (2)。我们发现成纤维细胞中 dmyc 替代了 c-myc，表明它们具有相似的生物学活性。这表明哺乳动物和昆虫控制身体大小的机制可能存在根本差异。我们认为，在哺乳动物中，c-Myc 控制着分裂或不分裂的决定，从而充当决定器官和身体大小的信号的关键调节者。
Overexpression of the proto-oncogene c-myc has been implicated in the genesis of diverse human tumours. c-Myc seems to regulate diverse biological processes, but its role in tumorigenesis and normal physiology remains enigmatic(1). Here we report the generation of an allelic series of mice in which c-myc expression is incrementally reduced to zero. Fibroblasts from these mice show reduced proliferation and after complete loss of c-Myc function they exit the cell cycle. We show that Myc activity is not needed for cellular growth but does determine the percentage of activated T cells that re-enter the cell cycle. In vivo, reduction of c-Myc levels results in reduced body mass owing to multiorgan hypoplasia, in contrast to Drosophila dmyc mutants, which are smaller as a result of hypotrophy(2). We rnd that dmyc substitutes for c-myc in fibroblasts, indicating they have similar biological activities. This suggests there may be fundamental differences in the mechanisms by which mammals and insects control body size. We propose that in mammals c-Myc controls the decision to divide or not to divide and thereby functions as a crucial mediator of signals that determine organ and body size.