Cell Proliferation and Cancer

The formation of many cells (multicellularity) from a single fertilized egg involves a complex, highly coordinated series of processes that include cell proliferation, cell quiescence, apoptosis, and activation of dormant cells by extracellular factors. After embryogenesis, under normal conditions, most of the cells are in a nondividing, quiescent state called G0. Some continue to divide as needed, and apoptosis ensures that there is not an excessive accumulation of cells in any tissue or organ (Figure 16.1). Dozens of different proteins are required to induce or constrain cell proliferation, maintain or prevent cell division cycles, and initiate or inhibit apoptosis. Cell proliferation is triggered by a cascade of activation and inactivation steps, which, for the most part, are mediated by protein kinases that phosphorylate tyrosine, threonine, or serine residues of cytoplasmic and nuclear proteins. The nuclear proteins usually are transcription factors that collectively regulate the expression of scores of genes. In addition to the proteins required for activation of cell proliferation, cell division cycle, and apoptosis, others that help stave off cancer are used to repair damage to genomic DNA.

Cancer is the all-inclusive term for unrestrained cell growth. Generally, a cancer cell is a somatic cell with accumulated mutations in different genes that collectively cause a loss of control of cell proliferation. As a consequence, a mass of cells (tumor) forms. Some tumors continue to grow at the original site, and others stop and recede. In the worst case, tumor cells can become migratory (metastasize) and move into other sites, where, quite often, cell proliferation occurs unabated. A tumor that invades other tissues is malignant, and one that remains at its original site is benign. The continuous growth of cancer cells leads to severe tissue damage, organ failure, and, eventually, death. To date, more than 200 types of cancer syndromes have been identified affecting almost

Induction of cell proliferation

Induction of cell proliferation

every type of cell, tissue, and organ system. A cancer often is classified according to its initial (primary) site of occurrence. About 85% of all cancers are carcinomas and arise from cells that line organs and form part of the skin; about 2% are sarcomas from cells of connective, bone, or muscle tissue; about 5% are lymphomas from white blood cells of the spleen and lymph nodes; and about 3% are leukemias from white blood cells (leukocytes) of the blood system. Cancers of glandular tissues are called adenocarcinomas; cancers of the nonneuronal cells of the brain are called gliomas and astrocytomas; and cancers of plasma cells are called myelomas.

Mutations of about 300 genes have been implicated in the formation and development of the vast array of different human cancers. About 20% and 90% of all cancers have germline and somatic mutations, respectively. Most germline cancer mutations have no effect unless a somatic mutation occurs in the other allele. Parenthetically, for cancer clinicians, the term "familial cancer" usually denotes a cancer that affects a number of members of a family and is not necessarily inherited, whereas "hereditary cancer" describes cancers that are inherited, and, in some instances, are familial. About 5% of all cancers are hereditary, with a germline mutation playing a major role (Table 16.1). In most hereditary cancer syndromes and in nearly all sporadic forms, a number of mutations in a somatic cell are required for the initiation and development of a cancer. In this context, cancer resembles an oligogenic trait.

The genetic basis of cancer is confounding, because different combinations of different mutant genes can give rise to the same type of cancer. Some gene mutations are common among different cancers, whereas others are confined to a specific cell type. Many of the mutations that lead to cancer occur spontaneously. Others are caused by chemical agents (carcinogens) in tobacco smoke, foods, and the workplace; by ultraviolet light and ionizing radiation; and by viruses that either commandeer the cell division process of a tissue or insert a viral genome into a locus responsible for cell proliferation.

In the United States, approximately 500,000 people die from cancer-based disorders annually, and more than 1 million new cases are diagnosed each year. Although only a small percentage of all cancers are hereditary, these examples have contributed significantly to current insights into the molecular aspects of these disorders. An understanding of how cancers arise depends on knowledge of the signal transduction pathways that induce cell proliferation, the proteins that control and constrain the cell division cycle, and the ways in which apop-tosis is kept in check.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

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