Oncogenes and Tumor Suppressor Genes
Oncogenes and Tumor
Suppressor Genes
We now recognize that cancer is a result of a series of specific genetic changes that take place in a particular clone of cells. These include alterations in two types of genes: oncogenes and tumor suppressor genes, and there are numerous specific genes of each type now known.
Oncogenes (Gr. onkos, bulk, mass; + genos, descent) are genes whose activity has been associated for some time with the production of cancer. They are genes that are normally found in cells, and in their normal form they are called proto-oncogenes. One of these codes for a protein known as Ras. Ras protein is a guanosine triphosphatase (GTPase) that is located just beneath the cell membrane. When a receptor on the cell surface binds a growth factor, Ras is activated and initiates a cascade of reactions, ultimately leading to cell division. The oncogene form codes for a protein that initiates the cell-division cascade even when the growth factor has not bound to the surface receptor, that is, the growth factor is absent.
Of the many ways that cellular DNA can sustain damage, the three most important are ionizing radiation, ultraviolet radiation, and chemical mutagens.The high energy of ionizing radiation (x rays and gamma rays) causes electrons to be ejected from the atoms it encounters, resulting in ionized atoms with unpaired electrons (free radicals). The free radicals (principally from water) are highly reactive chemically, and they react with molecules in the cell, including DNA. Some damaged DNA is repaired, but if the repair is inaccurate, a mutation results. Ultraviolet radiation is of much lower energy than ionizing radiation and does not produce free radicals. It is absorbed by pyrimidines in DNA and causes formation of a double covalent bond between the adjacent pyrimidines. UV repair mechanisms can also be inaccurate. Chemical mutagens react with the DNA bases and cause mispairing during replication.
Gene products of tumor suppressor genes act as a constraint on cell proliferation. One such product is called p53 (for “53-kilodalton protein,” a reference to its molecular weight). Mutations in the gene coding for p53 are present in about half of the 6.5 million cases of human cancer diagnosed each year. Normal p53 has a number of crucial functions, depending on the circumstances of the cell. It can trigger apoptosis, act as a transcription activator or repressor (turning genes on or off), control progression from G1 to S phase in the cell cycle, and promote repair of damaged DNA. Many of the mutations known in p53 interfere with its binding to DNA and thus its function.
We now recognize that cancer is a result of a series of specific genetic changes that take place in a particular clone of cells. These include alterations in two types of genes: oncogenes and tumor suppressor genes, and there are numerous specific genes of each type now known.
Oncogenes (Gr. onkos, bulk, mass; + genos, descent) are genes whose activity has been associated for some time with the production of cancer. They are genes that are normally found in cells, and in their normal form they are called proto-oncogenes. One of these codes for a protein known as Ras. Ras protein is a guanosine triphosphatase (GTPase) that is located just beneath the cell membrane. When a receptor on the cell surface binds a growth factor, Ras is activated and initiates a cascade of reactions, ultimately leading to cell division. The oncogene form codes for a protein that initiates the cell-division cascade even when the growth factor has not bound to the surface receptor, that is, the growth factor is absent.
Of the many ways that cellular DNA can sustain damage, the three most important are ionizing radiation, ultraviolet radiation, and chemical mutagens.The high energy of ionizing radiation (x rays and gamma rays) causes electrons to be ejected from the atoms it encounters, resulting in ionized atoms with unpaired electrons (free radicals). The free radicals (principally from water) are highly reactive chemically, and they react with molecules in the cell, including DNA. Some damaged DNA is repaired, but if the repair is inaccurate, a mutation results. Ultraviolet radiation is of much lower energy than ionizing radiation and does not produce free radicals. It is absorbed by pyrimidines in DNA and causes formation of a double covalent bond between the adjacent pyrimidines. UV repair mechanisms can also be inaccurate. Chemical mutagens react with the DNA bases and cause mispairing during replication.
Gene products of tumor suppressor genes act as a constraint on cell proliferation. One such product is called p53 (for “53-kilodalton protein,” a reference to its molecular weight). Mutations in the gene coding for p53 are present in about half of the 6.5 million cases of human cancer diagnosed each year. Normal p53 has a number of crucial functions, depending on the circumstances of the cell. It can trigger apoptosis, act as a transcription activator or repressor (turning genes on or off), control progression from G1 to S phase in the cell cycle, and promote repair of damaged DNA. Many of the mutations known in p53 interfere with its binding to DNA and thus its function.
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