Oncogenes, Tumor Suppressor Genes, and DNA Repair: Cancer Development
Oncogenes, Tumor Suppressor Genes, and DNA Repair Genes
Oncogenes
Oncogenes are altered (mutated) versions of normal genes that can promote malignant transformation. Normal genes, when not mutated, are called proto-oncogenes and usually promote growth. They can be growth factors, growth factor receptors, plasma kinases, or transcription factors. Oncogenes are a group of damaged genes involved in cancer development. Their presence, overactivity, or both, can stimulate cancer development. When oncogenes are present in normal cells, they can contribute to cancer development by instructing cells to produce proteins that stimulate excessive cell division and growth. They are related to the normal genes called proto-oncogenes, which encode components of the control mechanism of normal cell growth (growth factors, receptors, enzymes, and transcription factors). Oncogenes arise from mutations in proto-oncogenes and are similar in that they encode proteins involved in growth control. However, oncogenes encode altered versions (or excessive amounts) of these growth control proteins, thus altering the signaling mechanism of cell growth. To produce abnormal versions or quantities of proteins that control cell growth, oncogenes make the signaling mechanism of cell growth become hyperactive. A cancer cell may contain one or more oncogenes, which means that one or more components in this mechanism will be abnormal.
Tumor Suppressor Genes
Tumor suppressor genes are genes capable of preventing the transformation of normal cells into tumors by repairing DNA damage or inducing apoptosis in “non-repairable” cases. If they are functional, there is no cancer. Their absence may lead to cancer. They instruct cells to produce proteins that restrict growth and cell division. They encode proteins that slow cell growth and division; the loss of these proteins allows the cell to grow and divide uncontrollably. A particular tumor suppressor gene encodes a protein called “p53,” which can lead to cell suicide (apoptosis). In cells that have suffered damage to their DNA, the p53 protein acts as a “brake” that stops growth and cell division.
DNA Repair Genes
DNA repair genes are the third class of genes involved in cancer. They encode proteins whose normal function is to correct errors that arise when cells duplicate their DNA before dividing. Mutations in DNA repair genes can lead to a failure in DNA repair.
The Role of Genes in Cancer Development
Cancer can start due to the accumulation of mutations involving oncogenes, tumor suppressor genes, and DNA repair genes. For example, colon cancer can be initiated with a defect in a tumor suppressor gene that allows excessive cell proliferation. Proliferating cells tend to acquire subsequent mutations that include DNA repair genes, other tumor suppressor genes, and many other growth-related genes. Over time, the accumulated damage can produce a highly malignant, metastatic tumor. In other words, the formation of a cancer cell requires the brakes on cell growth (tumor suppressor genes) to be loosened at the same time as the accelerator for cell growth (oncogenes) is activated.