Schmandt R, Mills G B
Toronto General Hospital, Ontario, Canada.
Clin Chem. 1993 Nov;39(11 Pt 2):2375-85.
Many of the genes encoding growth factors, growth factor receptors, enzymes, and other effector molecules that regulate normal cell growth are designated protooncogenes. Oncogenes, those genes associated with cellular transformation, differ from their protooncogenic progenitors by being mutated, overexpressed, or expressed at inappropriate times or locations in the cell. One of the activities of growth factors is to prime cells to undergo programmed cell death, which is characterized by a series of morphologic changes called apoptosis. In normal cells, specific mediators must be activated or suppressed to bypass programmed cell death. In tumor cells, either the pathways leading to apoptosis are not functional or the mediators that normally "rescue" cells from this fate are overexpressed or constitutively activated. In addition to the biochemical pathways that drive cell division, there are others that limit cell proliferation; these, designated tumor suppressors, anti-oncogenes, or recessive oncogenes, must be inactivated in normal cells to allow passage through the cell cycle and cell proliferation. In contrast to oncogenes, which are overexpressed or activated in tumors, tumor-suppressor genes are frequently inactivated in tumor cells, either by mutation or deletion. Thus, in normal cells a series of checks and balances must be overcome to allow initiation and continuation of cell division. In tumors, these processes are aberrant, resulting in increased rates of cell division, increases in the proportion of cells in the cell cycle, or increased survival of activated cells. Therefore, tumor cells frequently accumulate genomic alterations, which may result in the activation of a particular array of oncogenes, the inactivation of specific tumor-suppressor genes, and the bypassing of programmed cell death. Trials of antitumor agents that act by exploiting the overexpression of oncogenes in tumors and of the biochemical pathways by which they mediate cell proliferation are currently underway.
许多编码生长因子、生长因子受体、酶以及其他调节正常细胞生长的效应分子的基因被称为原癌基因。癌基因，即那些与细胞转化相关的基因，与其原癌基因前身的不同之处在于发生了突变、过度表达，或者在细胞内不适当的时间或位置表达。生长因子的活动之一是促使细胞经历程序性细胞死亡，其特征是一系列称为细胞凋亡的形态学变化。在正常细胞中，必须激活或抑制特定的介质以绕过程序性细胞死亡。在肿瘤细胞中，要么导致细胞凋亡的途径不起作用，要么通常使细胞“免于”这种命运的介质过度表达或持续激活。除了驱动细胞分裂的生化途径外，还有其他限制细胞增殖的途径；这些被称为肿瘤抑制基因、抗癌基因或隐性癌基因，在正常细胞中必须失活才能使细胞通过细胞周期并进行细胞增殖。与在肿瘤中过度表达或激活的癌基因不同，肿瘤抑制基因在肿瘤细胞中经常因突变或缺失而失活。因此，在正常细胞中，必须克服一系列的制衡机制才能启动和持续细胞分裂。在肿瘤中，这些过程是异常的，导致细胞分裂速率增加、细胞周期中细胞比例增加或激活细胞的存活率增加。因此，肿瘤细胞经常积累基因组改变，这可能导致特定一系列癌基因的激活、特定肿瘤抑制基因的失活以及程序性细胞死亡的绕过。目前正在进行通过利用肿瘤中癌基因的过度表达及其介导细胞增殖的生化途径来发挥作用的抗肿瘤药物试验。
