Apoptosis and predisposition to oral cancer.
Apoptosis and predisposition to oral cancer.
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DOI：
10.1177/10454411990100020201
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
P. Polverini;J. Nör
中科院分区：
文献类型：
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作者：
P. Polverini;J. Nör
细胞凋亡，也被称为程序性细胞死亡(PCD)，是由发育生物学家在几年前创造的，描述一种以几种独特的形态和生化特征为特征的细胞死亡形式。对圆虫秀丽隐杆线虫(Caeneorhabditis Elegans)的遗传学研究首次揭示了细胞凋亡是发育过程中不可或缺的一部分。随后，在几个真核系统中，细胞凋亡在高等生物中的重要性被证明。在哺乳动物中，细胞凋亡在胚胎发育过程中和成年组织中普遍存在。它是正常组织动态平衡和免疫系统克隆选择所必需的。在发育中的生物体和成年生物体中，细胞凋亡在加强适当的细胞模式和通过消除有害或不再需要的细胞来调节细胞数量方面发挥着核心作用。越来越清楚的是，细胞凋亡途径的中断可导致许多发育性、炎症性、退行性和肿瘤性疾病的发生。凋亡程序的效应臂包括作为死亡激动剂或死亡拮抗剂的Bcl-2基因家族成员。这些蛋白质参与了一个复杂的基因控制的生化途径，该途径的功能是维持组织和器官的动态平衡，并作为防止恶性转化的关键防御机制。癌症是一系列遗传损伤的结果，包括癌基因的激活和肿瘤抑制基因的失活或丢失。几组研究人员已经观察到，癌基因的非调控表达可以颠覆凋亡途径，导致细胞存活时间延长。在癌症等病理环境中，Bcl-2基因家族的成员能够与癌基因和肿瘤抑制基因协同转化细胞。在这篇综述中，我们描述了哺乳动物细胞的凋亡过程，并确定了Bcl-2基因家族诱导和/或保护细胞免受凋亡的作用和生化途径。最后，我们将讨论表明这一途径的改变可能在肿瘤发生中发挥核心作用的证据，因为它允许通常注定要被消除的遗传损伤细胞持续存在，使它们容易发生额外的突变，并将它们驱动为恶性肿瘤。
The term apoptosis, also known as programmed cell death (PCD), was coined by developmental biologists a number of years ago to describe a form of cell death characterized by several unique morphological and biochemical features. Genetic studies of the round worm Caeneorhabditis elegans, a simple multicellular organism, first revealed apoptosis to be an integral part of the developmental program. Subsequently, the importance of apoptosis in higher organisms was demonstrated in several eukaryotic systems. [n mammals, apoptosis is widespread during embryogenesis and in adult tissues. It is required for normal tissue homeostasis and for clonal selection in the immune system. In both developing and adult organisms, apoptosis plays a central role in reinforcing appropriate cellular patterns and in regulating cell number by eliminating cells that are harmful or no longer needed. It is becoming increasingly clear that disruption in the apoptosis pathway can contribute to the development of a number of developmental, inflammatory, degenerative, and neoplastic diseases. The effector arm of the apoptotic program includes members of the Bcl-2 gene family that function as either death agonists or death antagonists. These proteins participate in an elaborate genetically controlled biochemical pathway that functions to maintain tissue and organ homeostasis and serve as a critical defense mechanism to guard against malignant transformation. Cancer is the result of a series of genetic lesions that include activation of oncogenes and inactivation or loss of tumor suppressor genes. Several groups of investigators have observed that deregulated expression of oncogenes can subvert apoptotic pathways, resulting in prolonged cell survival. In pathological settings such as cancer, members of the Bcl-2 gene family are able to synergize with oncogenes and tumor suppressor genes to transform cells. In this review, we describe the process of apoptosis in mammalian cells and define the role and biochemical pathways through which the Bcl-2 gene family induce and/or protect cells from apoptosis. Last, we will discuss the evidence which suggests that alterations in this pathway may play a central role in tumorigenesis by allowing genetically damaged cells normally destined for elimination to persist, predisposing them to additional mutations and driving them to malignancy.