Tumor-suppressor genes and cancer
Tumor-suppressor genes play a crucial role in regulating cell growth and division, maintaining cellular health, and preventing cancer. These genes function by controlling cell division, repairing DNA damage, and initiating programmed cell death (apoptosis) in cells with irreparable damage. When these genes are mutated, they can lose their ability to regulate cell growth, leading to an increased risk of tumor formation. Notably, both copies of a tumor-suppressor gene must usually be inactivated for significant cancer risk to arise, which is why inherited mutations in these genes often correlate with familial cancer syndromes.
Among the most critical tumor-suppressor genes are TP53 and RB1. The TP53 gene is involved in numerous cellular processes and is frequently inactivated in various cancers, including lung, breast, and colorectal cancers. Similarly, the RB1 gene regulates the cell cycle and is implicated in several cancer types, including retinoblastoma and lung cancer. The ongoing study of tumor-suppressor genes enhances understanding of cancer biology and informs the development of targeted therapies. Advances in genetic testing also help identify individuals at higher risk for certain cancers, allowing for proactive health management. This field remains vital in cancer research, offering hope for improved diagnosis and treatment options.
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Tumor-suppressor genes and cancer
DEFINITION: Tumor-suppressor genes are genes found in normal cells and function to control cell division, repair damage to deoxyribonucleic acid (DNA), and tell cells when to die. Mutated tumor-suppressor genes can cause a loss of growth control and lead to cancer.
What they do: Tumor-suppressor genes regulate cell division and growth through many biochemical mechanisms. The quality the mechanisms have in common is that the loss of each increases the likelihood that a cell will undergo a transformation from a normal cell to a cancerous one. Tumor-suppressor genes code for proteins that inhibit the division of cells if proper conditions for growth are not met. Conditions that could inhibit division include DNA damage, a lack of growth factors, or a malfunction of the cell’s division machinery. According to the Cleveland Clinic, scientists have identified around 1,000 tumor-suppressor genes. Other institutions place the number around seventy-three, although they allow many more are being identified.
Types of tumor-suppressor genes: There are several types of tumor-suppressor genes. Some control cell division and growth. The retinoblastoma (RB1) gene is an example of this type. A second type is involved in repairing errors in DNA. The process of DNA replication leads to occasional mistakes, and cells have a set of proteins that function to repair these mistakes. A third type is responsible for inducing a cell to undergo programmed cell death, or apoptosis, if its DNA is damaged beyond repair or if the cell division process malfunctions. In this way, the cell’s well-being is monitored, protecting the organism from the effects of runaway replication of wayward cells by activating the apoptotic pathway in such cells. The TP53 (also known as p53) gene is an example of this type of tumor-suppressor gene.
Because the presence of tumor-suppressor genes contributes to normal cell division and function, both copies of a tumor-suppressor gene must be inactivated to result in a maximum increased risk of cancer development. An increased risk of developing a specific type of cancer in some families is often the result of the presence of one defective copy of a tumor-suppressor gene. Although there is a low likelihood that the good copy of the tumor-suppressor gene will be mutated in any given cell, there is a much higher likelihood that the necessary second mutation will occur somewhere in the vast number of cells in a human body. Many of the identified tumor-suppressor genes are implicated in familial cancers. Inheritance of a defective copy of one of these genes carries a greatly increased risk of developing one or more specific cancer types, often otherwise rare. In some cases, mutant copies of these genes are linked to susceptibility to multiple cancer types, as with the retinoblastoma (RB1) gene. The two most critical tumor-suppressor genes code for the TP53 and retinoblastoma proteins (RB1 or pRB).
TP53 gene: The TP53 gene has been found to be involved in numerous cellular processes and is considered one of the most important cancer-related genes. The TP53 protein belongs to a class of proteins containing covalently bound phosphate groups, called phosphoproteins. It is located in the nucleus of the cell and interacts directly with the cell’s DNA to function as a transcription factor by binding to a specific DNA sequence in the control regions of the genes it controls. The number of bound phosphate groups modulates the activity of TP53. Normal TP53 function results in a global transcriptional response that can negatively regulate cell division or induce apoptosis. TP53 function is activated in response to various kinds of cell stress that increase the cell’s need for DNA repair and surveillance of the cell’s physiological status, including irradiation, lack of oxygen, oncogene activation, and DNA damage.
The TP53 gene is the single most frequently inactivated gene in human cancers. Between 70 and 90 percent of small-cell lung cancers, between 40 and 60 percent of breast cancers, and between 40 and 70 percent of colorectal cancers have been shown to be associated with mutant forms of TP53.
Retinoblastoma (RB1) gene: The RB1 gene encodes another phosphoprotein in the cell's nucleus. The RB1 protein acts as a negative regulator of cell division by binding to other transcription factors to alter their function. The action of these other transcription factors, in turn, regulates the expression level of several different genes. The number of phosphate groups bound to the RB1 protein controls its ability to bind to other transcription factors and varies in a regularly controlled manner during a normal cell cycle. The RB1 protein is responsible for a significant “checkpoint,” or regulatory step, in the cell cycle, in which cells must decide whether to undergo another round of cell division. Normal RB1 protein function results in a coordinated cell progression through the division process. Loss of the RB1 protein leads to unregulated and increased cell division, which is characteristic of cancer cells. The RB1 gene is mutated in many types of cancer, including retinoblastoma (a cancer of the eye from which the gene got its name), as well as bone, lung, breast, and bladder cancers.
The study of tumor-suppressing genes and cancer continues in the twenty-first century. Understanding concepts such as the frequency of mutations in genes, including p53, RB1, APC, BRCA1, BRCA2, PTEN, and INK4, and their role in cancer progression has allowed for more effective diagnosis and treatment of cancer patients. As researchers continue identifying novel tumor-suppressing genes, targeted therapies can be developed to treat the related cancers. Finally, advances in genetic testing have allowed doctors to more efficiently identify patients who may be at a higher risk of developing certain cancers.
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