Weinhouse S
Cancer. 1980 Jun 15;45(12):2975-80. doi: 10.1002/1097-0142(19800615)45:12<2975::aid-cncr2820451215>3.0.co;2-f.
A common thread interwoven throughout the literature of cancer biology is a wide-ranging abnormality of gene regulation, manifested by misprogramming of protein synthesis. This phenomenon encompasses virtually every means of identification of proteins, including antigens, hormones, growth factors, membrane components, and enzymes. Studies by the author and others of the activities of enzymes existing in multiple forms (termed isozymes) in a series of rat hepatomas ranging widely in growth rate, degree of differentiation, and other phenotypic properties has extended this concept and added to it a dimension of functional significance. Isozymes that are in high activity in adult liver and that are geared kinetically to catalyze specific hepatic functions are lost in varying degrees and generally depend on the growth rate and degree of differentiation. In fast growing, poorly differentiated hepatomas, these are replaced by high activities of isozymes that are normally low or absent in adult liver. In many instances, the isozymes that are expressed in poorly differentiated hepatomas are present also in fetal liver, thus pointing to reactivation of genes that were active in the fetus but were inactivated during normal embryonic development. The loss of isozymes that are under rigid host endocrine control, as well as other proteins that maintain the differentiated state, and the re-activation of genes coding for fetal or ectopic proteins are probably crucial factors in the initiation and maintenance of cellular proliferation.
贯穿癌症生物学文献的一个共同主线是基因调控的广泛异常，表现为蛋白质合成的编程错误。这种现象几乎涵盖了蛋白质识别的各种方式，包括抗原、激素、生长因子、膜成分和酶。作者及其他人对一系列生长速度、分化程度和其他表型特性差异很大的大鼠肝癌中以多种形式存在的酶（称为同工酶）的活性进行的研究扩展了这一概念，并赋予其功能意义的维度。在成年肝脏中具有高活性且在动力学上适合催化特定肝脏功能的同工酶在不同程度上丧失，并且通常取决于生长速度和分化程度。在快速生长、低分化的肝癌中，这些同工酶被成年肝脏中通常低活性或不存在的同工酶的高活性所取代。在许多情况下，低分化肝癌中表达的同工酶在胎儿肝脏中也存在，因此表明在胎儿期活跃但在正常胚胎发育过程中失活的基因被重新激活。受严格宿主内分泌控制的同工酶以及维持分化状态的其他蛋白质的丧失，以及编码胎儿或异位蛋白质的基因的重新激活可能是细胞增殖启动和维持的关键因素。
