Ewen M E
Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Cancer Metastasis Rev. 1994 Mar;13(1):45-66. doi: 10.1007/BF00690418.
Tumor formation results from alterations in the control of normal cell proliferation. To further our understanding of the molecular mechanisms underlying the deregulation of cell proliferation much attention, over the past decade, has been focused on the function of proto-oncogenes. Cellular oncogenes are thought to be growth promoting. More recently, a class of genes known as tumor suppressors have come under intense study. Tumor suppressors are largely thought to restrain cell proliferation. The retinoblastoma protein (Rb) is one of a growing list of tumor suppressors. Concurrent with the study of tumor suppressor genes has been a rapid increase in our understanding of the cell cycle at the molecular level. Rb and a related protein p107 are involved in the processes of cell proliferation and differentiation. Each functionally interacts with and affects the activity of the transcription factor E2F as well as other transcription factors involved in cell proliferation and differentiation. Additionally, Rb and p107 are modified by, and/or form specific complexes with, several elements of the basic cell cycle machinery. Specifically, Rb and p107 interact with and are modified by various cyclins and cyclin dependent kinases (cdk), some of which have been shown to be essential for cell cycle progression and in some cases their deregulation has been implicated in the development of cancer. This review will attempt to convey our current functional and mechanistic understanding of the biological roles Rb and p107 play in proliferation, development and differentiation. A knowledge of the interplay between these positive and negative regulators of cell proliferation and differentiation, noted above, is central to our understanding of human cancer.
肿瘤形成源于正常细胞增殖控制的改变。为了进一步了解细胞增殖失调背后的分子机制，在过去十年中，人们将大量注意力集中在原癌基因的功能上。细胞癌基因被认为具有促进生长的作用。最近，一类被称为肿瘤抑制基因的基因受到了深入研究。肿瘤抑制基因在很大程度上被认为能够抑制细胞增殖。视网膜母细胞瘤蛋白（Rb）是越来越多的肿瘤抑制基因之一。在对肿瘤抑制基因进行研究的同时，我们对细胞周期在分子水平上的理解也迅速增加。Rb和相关蛋白p107参与细胞增殖和分化过程。它们各自在功能上与转录因子E2F以及其他参与细胞增殖和分化的转录因子相互作用并影响其活性。此外，Rb和p107会被基本细胞周期机制的几个元件修饰，和/或与之形成特定复合物。具体而言，Rb和p107与各种细胞周期蛋白和细胞周期蛋白依赖性激酶（cdk）相互作用并被其修饰，其中一些已被证明对细胞周期进程至关重要，在某些情况下，它们的失调与癌症的发生有关。本综述将试图阐述我们目前对Rb和p107在增殖、发育和分化中所起生物学作用的功能和机制理解。如上文所述，了解这些细胞增殖和分化的正负调节因子之间的相互作用，对于我们理解人类癌症至关重要。
