Gilbert D A
Biosystems. 1977 Dec;9(4):215-28. doi: 10.1016/0303-2647(77)90006-5.
If the initiation/suppression of cell replication results from the operation of an intracellular switch, then proliferation control can be expected to occur through the modulation of its threshold setting or sensitivity. Assuming the existence of a threshold and the uptake of regulators by an equilibrium process, one can explain various types of dependency of the maximum cell density on the initial level of the regulator (e.g., serum) in the medium. Moreover it becomes theoretically possible to distinguish whether an altered threshold or equilibrium constant is responsible for modified proliferation characteristics. It is pointed out that some published data on transformed cells are more consistent with an altered threshold than the permeability change invoked. Other data suggests that transformation has produced more complex effects. The arguments presented indicate that while some cells may be more susceptible to control via changes in the relevant equilibrium constant, others may respond more markedly to threshold modulation. If control occurs through inhibition of replication, it is possible for the system to exhibit a critical "mass": if this is exceeded (in ways discussed) proliferation could continue indefinitely provided adequate nutrients are available. An oscillator concept of the cell cycle accounts for the existence of a threshold and also permits a general understanding of its modulation by multiple agents. It is concluded that at least some forms of cancer are the result of altered thresholds.
如果细胞复制的起始/抑制是由细胞内开关的运作引起的，那么增殖控制有望通过调节其阈值设置或敏感性来实现。假设存在一个阈值，且调节因子通过平衡过程被摄取，那么就可以解释最大细胞密度对培养基中调节因子（如血清）初始水平的各种依赖性。此外，从理论上讲，有可能区分改变的阈值或平衡常数是否导致了增殖特性的改变。需要指出的是，一些关于转化细胞的已发表数据与阈值改变比与所提出的通透性变化更为一致。其他数据表明转化产生了更复杂的影响。所提出的论据表明，虽然一些细胞可能更容易通过相关平衡常数的变化受到控制，但其他细胞可能对阈值调节反应更明显。如果控制是通过抑制复制来实现的，那么系统有可能表现出一个临界“质量”：如果超过这个临界值（以所讨论的方式），只要有足够的营养物质，增殖就可能无限期持续下去。细胞周期的振荡器概念解释了阈值的存在，也有助于对其被多种因素调节的总体理解。得出的结论是，至少某些形式的癌症是阈值改变的结果。
