Chapter 22
Cancer as a Genetic Dia
Key Concepts
Normal cell proliferation is modulated by cell cycle regulation.
Apoptosis is a normal lf-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 ries of special mutations in the same somatic cell.
Many of the class of genes that are mutated to cau 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) u steroids and other low-molecular-weight hormones as allosteric effectors of transcriptional regulatory molecules to coordinate appropriate respons 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.
秋风的词语In this chapter and the next one, we shall e this theme exploited in a variety of situation
s: 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 class of mutations to produce uncontrolled proliferation—the dias that we call cancers.
Cancer and the control of cell number: an overview炖冬瓜的家常做法
Cancer is now clearly understood as a genetic dia of somatic cells. In cancer, the fail-safe mechanisms that are in place to ensure that cell number remains balanced to the needs of the whole organism are subverted, and cancerous cells proliferate out of control. To understand how cells can mutate to a cancerous state, we must first understand the basic mechanisms governing the control坐下英语怎么说 of normal cell numbers.
Machinery of cell proliferation
Certain aspects of proliferation control are general to all organisms. Universally, the cell division process has numerous events that must take place quentially to produce viable progeny cells. Moreover, the cell division cycle has evolved so that there are checks and balances to prevent a subquent event from taking place before the prerequisite events have been achieved. For example, it would be a lethal event if mitosis occurred before DNA replication was completed. Mechanisms have evolved that prevent such cellular disasters. We shall explore the regulation of the eukaryotic cell cycle. Protein kinas, enzymes that specifically phosphorylate certain amino acid residues on target proteins, and protein phosphatas, enzymes that specifically remove phosphate groups from such amino acid residues, modulate the activities of key proteins in the cell division cycle. The phosphorylation–dephosphorylation pathways ultimately converge to determine which key proteins are active for a fraction of the entire cell division cycle. Put another way, it is the cyclical variations in the key proteins that determine which parts of the cell cycle are currently being executed.
老虎尾Machinery of cell death
时运变迁Some aspects of cell control appear to have evolved only in multicellular organisms. To develop and maintain themlves normally, multicellular organisms must properly balance the numbers of the cell types in their various tissues. Almost all of the cell types are somatic—that is, they do not contribute to the germ line. Loss of such somatic cells is not a problem for the organism from the point of view of propagation of the species, as long as proliferation of the remaining cells of that type in a particular tissue compensates for the cells that are eliminated. Furthermore, abnormal cells have the potential to do considerable harm. Thus, mechanisms have evolved to eliminate certain cells—through a process called programmed cell death or apoptosis. A cascade of enzymes called caspas kill by disrupting numerous structural and functional systems within the cell. Subquently, the carcass of the dead cells are removed by scavenger cells.胡乱之母
Linking cell proliferation and death to the environment
The cell proliferation and cell death machinery must be interconnected so that each is activated only under the appropriate environmental circumstances. For example, in adult organs, maintenance of proper cell 体育社团number requires proper balance between the birth of new cells and the loss of existing ones. Eukaryotic cells have evolved elaborate intercellular signaling pathways to rve as status indicators of the environment. Some signals stimulate proliferation, whereas others inhibit it. Furthermore, other signals can activate apoptosis, whereas still others block activation. Intercellular signaling pathways typically consist of veral components: the signals themlves, the receptors that receive the signals, and the signal transduction systems responsible for relaying the signal to various regions of the cell. Just as allosteric effectors regulate the activity of many DNA-binding proteins in bacteria, modifications to the various components of the intercellular signaling systems—protein phosphorylation, allosteric interactions between proteins and small molecules, or interaction between protein subunits—control梦绕魂牵的意思 the activity of the pathways.
