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Some of the known steps in converting a normal colon cell into a cancerous one. At least four known genes are involved, two oncogenes (APC and ras) and two tumor-suppressor genes (DCC or DPC4 or JV18 and p53). (Reprinted from Cell,
Vol. 87, K. W. Kinzler and B. Vogelstein, Lessons from Hereditary Colorectal Cancer, pp. 159 170, Copyright 1996, with permission from Elsevier Science.)
Tamarin: Principles of Genetics, Seventh Edition
III. Molecular Genetics
16. Gene Expression: Control in Eukaryotes
The McGraw Hill Companies, 2001
Sixteen
Gene Expression: Control in Eukaryotes
In summary, all cancers share the following traits. First, they provide their own growth signals while ignoring inhibitory signals; in essence, cancer cells can grow without limit. Second, cancer cells avoid apoptosis. Third, tumor cells create new blood supplies by a process known as angiogenesis; new blood vessels grow in the tumors, allowing them unlimited increase in size. And nally, all malignant tumors have the capability of invasive growth and metastasis.
IMMUNOGENETICS
Vertebrates have evolved the ability to protect themselves against invading bacteria, viruses, and parasites and against their own cancer cells by creating an enormous amount of immune diversity with relatively few genes. Here we concentrate on the genetic control of immunity, the ability of an animal to resist infection. The foreign substance from the bacterium, virus, parasite, or cancer cell that evokes an immune response is called an antigen. The immune response itself is a complex interaction of various cell types, signaling pathways, and other components. The immune system of a mammal can destroy millions of different antigens without harming its own cells quite an amazing accomplishment. The two major components of the immune system are the B and T lymphocytes, white blood cells that originate in bone marrow and mature in either the bone marrow (B cells) or the thymus gland (T cells). The B cells are responsible for producing very speci c proteins called antibodies, or immunoglobulins (Igs), which protect the organism from antigens in three general ways. Immunoglobulins can coat antigens so that they are more readily engulfed by phagocytes (white blood cells that engulf foreign material); immunoglobulins can combine with the antigens for example, by covering the membrane-recognition sites of a virus and thereby directly prevent their ability to function; or, in combination with complement, a blood component, immunoglobulins can cause the cell to die if the antigen is from an intact cell. B cells are the major component of humoral immunity, immunity controlled by antibodies in the serum and lymph; T cells are the major component of cellular immunity, immunity against infected cells. Whereas the B cells produce immunoglobulins, one type of T cell is concerned with locating and destroying infected cells to prevent invading organisms from escaping detection within those infected cells. The cytotoxic T lymphocytes attack host cells infected by a virus, bacterium, or parasite. Thus, infected cells are destroyed before new viruses, bacteria, or parasites can be produced, helping to terminate the infection. Cytotoxic T lymphocytes recognize infected host cells by surface receptors called T-cell receptors. These receptors recognize an infected host cell by two aspects of the infected cell s surface: major histocompatibility complex (MHC) gene products, and antigens. All host cells have MHC components on their surfaces; an infected cell has the ability to cause part of the antigen to appear on its surface with the MHC protein, as if the MHC protein were presenting the antigen to the T-cell receptor ( g. 16.31).
Environmental Causes of Cancer
Environment plays a major role in carcinogenesis, and many environmental carcinogenic agents are known (table 16.5). Many of these agents are also mutagens (see chapter 12). Avoidable substances in the environment and the diet are estimated to cause 80 to 90% of all cancers, although the exact mechanisms by which these agents induce transformation are generally unknown. Perhaps the most effective cancer prevention strategy would be to avoid as many carcinogens from the environment as possible. In the nal section of the chapter, Immunogenetics, we look at another genetic system of transcriptional control. We try to answer the question: How does a single organism produce such a vast array of immunological protection
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