遗传分析-第二十二章Cancer as a Genetic Disease.docVIP

Chapter 22 Cancer as a Genetic DiseaseKey Concepts Normal cell proliferation is modulated by cell cycle regulation. Apoptosis is a normal self-destruction mechanism that eliminates damaged and potentially harmful cells. Signaling systems permit proliferation and apoptosis to be coordinated within a population of cells. In cancer, cells proliferate out of control and avoid fail-safe destruction mechanisms through the accumulation of a series of special mutations in the same somatic cell. Many of the classes of genes that are mutated to cause cancers are important components of the cell that directly or indirectly contribute to growth control and differentiation. Introduction In Chapter 11, we learned about some ways in which a cell monitors its status relative to its environment and responds accordingly. For example, by utilizing certain metabolites as allosteric effectors of transcriptional regulatory proteins, an E. coli cell can make decisions about which sugar metabolic pathways to implement at any given time. Metazoa (multitissued animals) use steroids and other low-molecular-weight hormones as allosteric effectors of transcriptional regulatory molecules to coordinate appropriate responses of different organs to a particular physiological event. A major point to remember is that cells have evolved mechanisms that modulate the activity of key target proteins by relatively minor modifications—in the two preceding examples, by forming complexes with allosteric effectors. Much of genetics, indeed much of the biology of a cell, depends on such modulations, in which key proteins are toggled between active and inactive states. In this chapter and the next one, we shall see this theme exploited in a variety of situations: control of cell numbers, control of developmental pathways, and formation of complex biological patterns. In this chapter, we focus on how such modulations achieve proper control of cell number and how the systems can be overcome by certain classes o