Smilenov Lubomir B
Department of Radiation Oncology, College of Physicians and Surgeons, Center for Radiological Research, Columbia University, 630 w 168th St, New York, NY 10032, USA.
Cancer Lett. 2006 Aug 18;240(1):17-28. doi: 10.1016/j.canlet.2005.08.015. Epub 2005 Oct 11.
According to the current models, tumor development is a continuous process of mutation accumulation, leading to several intermediate phenotypes and final phases of autonomy, unlimited growth and metastasis. One of the most important events in that process is the initial destabilization of cellular pathways that subsequently allow mutations to accumulate. The mechanisms involved in that stage are not clear. In principle, the estimated very low mutation frequency in human or mouse cells would suggest that accumulating the required number of mutations for tumor development should be a statistically unlikely event. However, this theory is contradicted by the high incidence of cancers. Here we discuss the role of protein haploinsufficiency as a contributor to the initial phases of tumor development, and suggest possible mechanisms that might be involved in that process.
根据当前模型，肿瘤发展是一个突变积累的连续过程，会导致几种中间表型以及自主性、无限生长和转移的最终阶段。该过程中最重要的事件之一是细胞通路的初始不稳定，这随后会使突变得以积累。该阶段所涉及的机制尚不清楚。原则上，据估计人类或小鼠细胞中极低的突变频率表明，积累肿瘤发展所需数量的突变在统计学上应该是不太可能发生的事件。然而，癌症的高发病率与这一理论相矛盾。在此，我们讨论蛋白质单倍剂量不足在肿瘤发展初始阶段所起的作用，并提出该过程可能涉及的机制。
