Suppression of tumorigenicity by the cell-cycle-dependent control of cellular differentiation and proliferation.
Suppression of tumorigenicity by the cell-cycle-dependent control of cellular differentiation and proliferation.
复制标题
通过细胞周期依赖性细胞分化和增殖的控制来抑制致瘤性。
DOI：
10.1002/ijc.2910370613
复制
发表时间：
1986
影响因子：
6.4
通讯作者：
Scott,RE
中科院分区：
文献类型：
--
作者：
WilleJr,JJ;Scott,RE
本报告中描述的实验旨在确定致瘤性的抑制是否可以由控制3 T3 T型间充质干细胞细胞分化和/或增殖的细胞周期依赖性机制介导。使用这些细胞是因为它们具有独特的、充分表征的细胞周期依赖性机制来控制细胞分化和增殖。为了实现我们的目标，我们通过非诱变程序开发了23种3 T3 T干细胞的克隆变体，这些变体表达4种不同表型之一，用于调节细胞分化和增殖。6个克隆表达了分化和增殖控制的组合缺陷; 6个表达了完整的增殖控制机制，但分化控制缺陷; 3个表达了完整的分化控制机制，但增殖控制缺陷。最后，8个克隆在分化或增殖的对照中没有表达可检测的表型缺陷。一旦分离和表征，就测定这些克隆中的每一个的致瘤潜力。结果表明，表达分化和增殖控制中的组合缺陷的克隆是高度致瘤性的。相比之下，在保持控制其增殖或分化的能力的克隆中，致瘤性被显著抑制。此外，保持控制增殖和分化的能力的克隆没有显示出致瘤性的证据。这些数据被解释为表明细胞分化和/或增殖的严格调节控制可以作为癌症抑制机制。
The experiments described in this report were designed to determine if suppression of tumorigenicity can be mediated by cell‐cycle‐dependent mechanisms that control cellular differentiation and/or proliferation in mesenchymal stem cells of the 3T3 T type. These cells were employed because they possess distinct, well‐characterized cell‐cycle‐dependent mechanisms to control both cellular differentiation and proliferation. To achieve our goal we developed by non‐mutagenic procedures 23 clonal variants of 3T3 T stem cells that expressed one of 4 distinct phenotypes for the regulation of cellular differentiation and proliferation. Six clones expressed combined defects in the control of differentiation and proliferation; 6 expressed intact mechanisms to control proliferation but defects in the control of differentiation; and 3 expressed intact mechanisms to control differentiation but defects in the control of proliferation. Finally, 8 clones expressed no detectable phenotypic defects in the control of either differentiation or proliferation. Once isolated and characterized, each of these clones was assayed for its tumorigenic potential. The results establish that clones which express combined defects in the control of differentiation and proliferation are highly tumorigenic. By contrast, tumorigenicity is markedly suppressed in clones that maintain the ability to control their proliferation or their differentiation. Furthermore, clones that maintained the ability to control both proliferation and differentiation showed no evidence of tumorigenicity. These data are interpreted to suggest that stringently regulated control of cellular differentiation and/or proliferation can act as a cancer suppressor mechanism.