Rasnick D
Department of Molecular and Cell Biology, 229 Stanley Hall, University of California at Berkeley, Berkeley, CA 94720, USA.
Biochem J. 2000 Jun 15;348 Pt 3(Pt 3):497-506.
Evidence continues to accumulate that aneuploidy, an imbalance in the number of chromosomes, is responsible for the characteristic phenotypes of cancer, including the abnormal cellular size and morphology of cancer cells, the appearance of tumour-associated antigens, as well as the high levels of membrane-bound and secreted proteins responsible for invasiveness and loss of contact inhibition. Aneuploidy has also been demonstrated to be the self-perpetuating source of the karyotypic instability of cancer cells. Here it is shown that the auto-catalysed progression of aneuploidy explains the kinetics of the finite lifetime of diploid cells in culture, the time course of the appearance of papillomas and carcinomas in benzo[a]pyrene-treated mice, and the age-dependence of human cancers. Modelling studies indicate that the ease of spontaneous transformation of mouse cells in culture may be due to a chaotic progression of aneuploidy. Conversely, the strong preference towards senescence and resistance to transformation of human cells in culture may be the result of a non-chaotic progression of aneuploidy. Finally, a method is proposed for quantifying the aneuploidogenic potencies of carcinogens.
越来越多的证据表明，非整倍体，即染色体数量的失衡，是癌症特征性表型的原因，包括癌细胞异常的细胞大小和形态、肿瘤相关抗原的出现，以及负责侵袭性和接触抑制丧失的高水平膜结合蛋白和分泌蛋白。非整倍体也被证明是癌细胞核型不稳定的自我延续来源。本文表明，非整倍体的自催化进展解释了培养中双倍体细胞有限寿命的动力学、苯并[a]芘处理小鼠中乳头状瘤和癌出现的时间进程，以及人类癌症的年龄依赖性。模型研究表明，培养中小鼠细胞自发转化的容易程度可能是由于非整倍体的混沌进展。相反，培养中人类细胞对衰老的强烈偏好和对转化的抗性可能是非整倍体非混沌进展的结果。最后，提出了一种量化致癌物非整倍体诱导能力的方法。
