Cancer and Cell Death

Cancer and Cell Death                                     Understanding Cancer
One of the biggest paradoxes in medicine is cancer. Cancer results from the unregulated control of cell division, and cancer cells are therefore very successful in their ability to propagate. Yet their success is often the demise of the organism that they inhabit. This topic explores the differences between cancer cells and normal cells, as well as how cells die through either necrosis or programmed cell death. Cancer cells can be recognized from normal cells in many different ways. The best distinguishing difference between the two types is their growth in soft agar. Soft agar is a semisolid medium that encourages the division of cancer cells but not most normal cells. Cancer cells survive better in soft agar because they are less dependent than normal cells on attaching to a substratum. Normal cells secrete fewer proteases than cancer cells and have a more organized cytoskeleton. Normal cells grown in culture are mortal, usually succumbing after 25 to 50 divisions.
Cancer cells, by definition, are immortal and can divide continuously in culture as long as they are given a continuous supply of nutrients. Finally, cancer cells, but not normal cells, can cause tumors when injected into the appropriate animal host. Normal cells can be converted to cancer cells through a variety of mechanisms. Radiation such as ultraviolet light and X rays can cause mutations in DNA that in turn can cause unregulated cell division. Viruses can cause a variety of human cancers by introducing their DNA into the human genome and altering its function. Chemical carcinogens in the environment can cause cancer by binding to bases. A few compounds that are not carcinogens can be mistakenly converted to carcinogens in the liver. Spontaneous mutations can occur that result in a base change. If this alteration is not corrected by one of the myriad DNA correction enzymes, it could lead to altered genetic activity and cancer. No matter how a normal cell is converted to a cancer cell, however, some stable type of gene alteration must occur. One of these changes is the conversion of a protooncogene, a gene in normal cells that functions during cell growth and division, to an active oncogene, a gene whose activity results in cell transformation from the normal phenotype to a cancer cell. A variety of oncogenes that have been identified. Some are growth factor oncogenes such as the sis oncogene, whose product is platelet-derived growth factor. Other oncogenes, have protein products that are in the form of altered growth factor receptors. An example is the erbB oncogene, whose oncoprotein is a modified version of the epidermal growth factor. Many of these oncoproteins are receptors that can't be regulated by an external stimulus and, as such, are constitutively turned on. Other oncogenes work as intracellular transducers. One such oncogene, src, produces an oncoprotein that, as a protein kinase, phosphorylates tyrosine residues. Other oncogenes in this family work through Ras. Nuclear transcription factor oncogenes also exist by regulating transcription. But the group of oncogenes that causes more than half of all human cancers belong in the cell cycle control group and are called tumor suppressor genes.