c-Myc enhances protein synthesis and cell size during B lymphocyte development

c-Myc enhances protein synthesis and cell size during B lymphocyte development
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DOI:
10.1073/pnas.96.23.13180
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发表时间:
1999-11-09
影响因子:
11.1
通讯作者:
Eisenman, RN
Eisenman, RN
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Iritani, BM;Eisenman, RN

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核原癌基因的myc家族成员在细胞增殖、分化和凋亡中发挥作用。此外,c-myc基因的不适当表达有助于许多类型癌症的发展,包括人类的B细胞淋巴瘤。虽然Myc蛋白已被证明作为转录因子发挥作用,但它们对细胞的直接影响尚未得到很好的定义。在这里,我们已经利用了小鼠模型的淋巴瘤(E mu-myc小鼠),以显示组成型表达的c-myc转基因的控制下的IG重链增强子(E mu)的结果在正常的预转化的B淋巴细胞在B细胞发育的所有阶段的细胞大小的增加。此外,我们发现c-Myc诱导的生长独立于细胞周期阶段,并与蛋白质合成的增加相关。这些结果表明,Myc可能通过协调生长相关基因的表达来响应有丝分裂信号而正常发挥功能。c-myc表达失调可能通过增强细胞生长到无限制细胞分裂所需的水平而易患癌症。
Members of the myc family of nuclear protooncogenes play roles in cell proliferation, differentiation, and apoptosis, Moreover, inappropriate expression of c-myc genes contributes to the development of many types of cancers, including B cell lymphomas in humans. Although Myc proteins have been shown to function as transcription factors, their immediate effects on the cell have not been well defined. Here we have utilized a murine model of lymphomagenesis (E mu-myc mice) to show that constitutive expression of a c-myc transgene under control of the Ig heavy-chain enhancer (E mu) results in an increase in cell size of normal pretransformed B lymphocytes at all stages of B cell development. Furthermore, we show that c-Myc-induced growth occurs independently of cell cycle phase and correlates with an increase in protein synthesis. These results suggest that Myc may normally function by coordinating expression of growth-related genes in response to mitogenic signals. Deregulated c-myc expression may predispose to cancer by enhancing cell growth to levels required for unrestrained cell division.