A group of proteins known as the cyclins promote different phases of the cell cycle. During the Gi phase of the cycle, for example, an increase in the concentration of cyclin D proteins within the cell acts to move the cell quickly through this phase. Cyclin D proteins do this by activating a group of otherwise inactive enzymes known as cyclin-dependant kinases. Therefore, overactivity of a gene that codes for a cyclin D might be predicted to cause uncontrolled cell division, as occurs in a cancer. Indeed, overexpression of the gene for cyclin D1 has been shown to occur in some cancers, including those of the breast and esophagus. Genes that contribute to cancer are called onco-genes. Oncogenes are mutated forms of normal genes, called proto-oncogenes, that are functional in normal, healthy cells.
While oncogenes promote cancer, other genes—called tumor suppressor genes—inhibit its development. One very important tumor suppressor gene is known as p53. This name refers to the protein coded by the gene, which has a molecular weight of 53,000. The normal gene protects against cancer by indirectly blocking the ability of cyclins to stimulate cell division. In part, p53 accomplishes this by inducing the expression of another gene, called p21, which produces a protein that binds to and inactivates the cyclin-dependant kinases. The p21 protein thus inhibits cell division as it promotes cell differentiation (specialization).
For these reasons, cancer is likely to develop if the p53 gene becomes mutated and therefore ineffective as a tumor suppressor gene. Indeed, mutated p53 genes are found in over 50% of all cancers. Mice whose p53 genes were "knocked out" all developed tumors. (Knockout mice are strains of mice in which a specific
■ Figure 3.27 The life cycle of a cell. The different stages of mitotic division are shown; it should be noted, however, that not all cells undergo mitosis.
One (duplicated) chromosome
One (duplicated) chromosome
■ Figure 3.28 The structure of a chromosome after DNA replication. At this stage, a chromosome consists of two identical strands, or chromatids.
targeted gene has been inactivated by developing the mice from embryos injected with specifically mutated cells.) These important discoveries have obvious relevance to cancer diagnosis and treatment.
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