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P53 gene

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Related terms
Background
Methods
Research
Implications
Limitations
Safety
Future research
Author information
Bibliography

Related Terms
  • Cancer, gene therapy, genetic mutation, Li-Fraumeni syndrome, molecular diagnosis, molecular genetics, mutation detection, oncosuppressor gene, p53, tumor suppressor.

Background
  • Genes are found inside the cells of all organisms. They are located within a defined space called the nucleus. An individual's genes are contained in a large molecule called DNA (deoxyribonucleic acid). A single gene is made of a specific sequence of nitrogen molecules called bases within a DNA molecule. The DNA is organized into 23 pair or 46 individual chromosomes. The total genetic composition of an individual is called the complete human genome. The human genome is made up of about 30,000 genes and a large quantity of DNA with other functions.
  • Genes provide instructions for making proteins. Proteins are the predominant molecules that form the structure of cells. They are responsible for the many functions that go on within the body.
  • A genetic disease or disorder is caused by abnormal expression of one or more genes, meaning the gene produces an abnormal protein or an abnormal amount of protein. This occurs when the chemicals that make up an individual's genes are incorrectly deleted, added, or substituted. Abnormal gene expression may also occur when there are mutations in areas of the DNA that do not code for genes, but that help to control how and when they function.
  • The cell cycle describes the growth and division of a cell. Some cells of the body, such as those of the skin, continuously grow and divide to replace dead or damaged cells. These cells are constantly in the cell cycle. Some cells of the body, such as nerve cells, do not divide regularly and are rarely, if ever, in the cell cycle.
  • The cell cycle is tightly regulated by proteins that direct when and if a cell enters the cycle, how quickly it proceeds, and how long it continues to replicate. This means that normal cells replicate only when additional cells are needed and stop replicating when they are not needed.
  • One of the proteins that controls the cell cycle is p53. It is present in low levels in healthy or non-stressed cells and in high levels when stress occurs. When a cell is stressed, p53 prevents it from continuing through the cell cycle. Types of cell stress that cause p53 to become active include excessive heat; too much or too little oxygen; damage to the DNA, proteins, or other important molecules; and the presence of external molecules that signal the cell to stop dividing. When it is damaged beyond repair, p53 can also induce cell death. This "programmed cell death" is called apoptosis.
  • Mutations in the gene that codes for the p53 protein can cause the protein to be absent or inactive. When this happens, the cell cycle may proceed out of control, or a damaged cell may continue to survive indefinitely. Cancer occurs when cells reproduce at a rate faster than they should or die off at a rate slower than they should. Cancer cells may also fail to respond to normal environmental cues, such as molecules from other cells that signal them to stop dividing. The ultimate result is too many of a single type of cell. Because normal p53 prevents the development of cancer, it is called a tumor suppressor gene or "oncosuppressor gene."
  • A mutation in p53 alone does not cause cancer. Cancer occurs when there are mutations in several different genes involved in the cell cycle. However, the p53 gene is the most commonly mutated gene in human cancers, occurring in about 40% of tumors. Therefore, detection of mutations in the p53 gene may be used to diagnose cancer or to determine its severity. Because mutations in the p53 gene are present in cancer cells but not in normal cells, it may become possible to treat cancer by targeting this gene. This may be done with gene therapy or molecules that specifically act on the mutated gene or protein.
  • Li-Fraumeni syndrome is an inherited mutation in the p53 gene. The only symptom associated with this syndrome is cancer, which may develop in many different organs at a young age.

Methods
  • Polymerase chain reaction: Polymerase chain reaction (PCR) is a method of multiplying a small piece of DNA millions of times so that it can be studied. With PCR, small segments of DNA that would otherwise be insufficient for diagnosis can be used to detect genetic mutations. PCR allows scientists at laboratories to determine if a mutated p53 gene is present even in a very small sample of tissue. It can also tell how much of the gene is present when it is performed with fluorescent probes in a process call real-time PCR (RT-PCR).
  • To perform PCR, cells are collected from a patient's blood, saliva, or tissues such as a tumor. A probe, or sequence of DNA that recognizes the p53 gene, is added to the patient's DNA. The probe may attach to normal or mutated p53 depending on how it is designed. After the probe attaches to the gene, proteins are added that make millions of copies of the gene.
  • Tissue staining: Tissue staining is an indirect method of detecting gene variants and is usually used on tissue that has been surgically removed, such as a tumor. The tumor is examined microscopically, and a stain is used to identify the p53 protein. If there is a large amount of the p53 protein present within the cell due to a genetic mutation, the stain will be very strong. However, if the p53 gene is not mutated and the cells are not abnormal, the stain will be very faint or absent.
  • Gene therapy: Gene therapy is a method of inserting a gene into a patient's tissue. It is currently only used in research. Genes are inserted into a patient through the use of a "vector," which carries the DNA. Vectors used in this method are usually viruses. Scientists change the genetic makeup of a viral vector so it carries normal human DNA instead of viral DNA. In other words, the virus' disease-causing genes are removed, and normal human genes are inserted.
  • When the vector enters the human body, it enters the body's cells. The normal genes in the virus replace the mutated genes in the patient. As a result, the new gene functions appropriately, and the patient's disorder or illnesses is treated.

Research
  • Current areas of research include the use of p53 to provide diagnosis, prognosis, and therapeutic interventions in cancer patients.
  • Diagnosis: Mutations in the p53 gene are present in about 40% of human cancers, making it the most common genetic mutation in cancer. Research is currently focusing on using these mutations to accurately diagnose cancer. Currently, p53 testing is not used alone to diagnose cancer but may be used with a variety of other methods to determine if cancer cells are present.
  • Prognosis: Prognosis is a prediction of how a disease will progress. Some researchers are trying to determine if p53 mutations or the amount of the p53 protein can be used to predict the future course of cancer in individual patients.
  • Therapeutic interventions: Because p53 mutations are so common in tumors, it may be possible to design treatments that target the p53 gene or protein. Drugs that attach to the gene or protein and affect how it functions may be able to change its activity back to normal and thus control the cancer cells. According to the U.S. government Web site, www.clinicaltrials.gov, there is currently a lack of drugs in clinical development that can affect p53 function. Research is currently being performed in laboratories on isolated cells and animal models.
  • Gene therapy is the introduction of new genes into the human body. Research is currently being conducted to determine if insertion of a normal p53 gene can correct the abnormal activity present in cancer cells. Currently, this research is limited to animal studies.

Implications
  • Currently, p53 is not used to diagnose or treat cancer. In the future, as researchers understand more about the gene and how to control it, it may be possible to treat cancer patients with gene therapy or drugs that specifically target mutated p53 genes. These drugs may be more effective and have fewer side effects than certain conventional treatment options.
  • By understanding the many different functions of p53 and how it interacts with other genes and proteins, it may be possible to develop treatments that target the genes and proteins that interact with p53 to control the cell cycle.

Limitations
  • There are many different mutations that can be present in the p53 genes. However, it is not currently possible to create a single genetic test that can detect all of the different possible mutations.
  • Gene therapy is still in its early experimental stages. General use is a long way off. There are many unknowns about gene therapy and its long-term effects.

Safety




Future research
  • Future research will continue to focus on the use of p53 in the diagnosis and treatment of cancer. In particular, using gene therapy or small molecules to target the p53 gene or protein will be researched heavily in the future.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. Bray SE, Schorl C, Hall PA. The challenge of p53: linking biology, biochemistry and patient management. Stem Cells. 1998;16:248-260.
  2. Cheah PL, Looi LM. P53: an overview of over two decades of study. Malays J Pathol. 2001;23(1):9-16.
  3. Gonzales K, Fong C, Buzin C, et al. P53 testing for Li-Fraumeni and Li-Fraumeni-like syndromes. Curr Protoc Hum Genet. 2008 Apr;Chapter 10:Unit 10.10.
  4. Hall PA. p53: The challenge of linking basic science and patient management. Oncologist. 1998;3:218-224.
  5. Koshland DE. Molecule of the year. 1993 Dec 24;262(5142):1953.
  6. Kuribayashi K, El-Deiry WS. Regulation of programmed cell death by the p53 pathway. Adv Exp Med Biol. 2008;615:201-21.
  7. National Center for Biotechnology Information. . Accessed May 31, 2008.
  8. Natural Standard: The Authority on Integrative Medicine. . Copyright © 2008. Accessed May 31, 2008.
  9. Selivanova G. p53: Fighting cancer. Curr Cancer Drug Targets. 2004 Aug;4(5):385-402.
  10. Wang W, El-Deiry WS. Restoration of p53 to limit tumor growth. Curr Opin Oncol. 2008;20(1):90-6.
  11. Wood YL, Lane DP. Exploiting the p53 pathway for cancer diagnosis and therapy. Hematol J. 2003;4(4):233-47.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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