tumor suppresor genes

tumor suppresor genes

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  Tumor Suppresor Gene By KAUSHALKUMAR SAHU Assistant Professor (Ad Hoc) Department of Biotechnology Govt. Digvijay Autonomous P. G. College Raj-Nandgaon ( C. G. )
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  Contents  Introduction  Two-hithypothesis  History  Functions  Examples  References
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  Introduction  A tumorsuppressor gene, or antioncogene, is a gene that protects a cell from one step on the path to cancer.  When this gene mutates to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.
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  Two-hit hypothesis  Unlikeoncogenes, tumor suppressor genes generally follow the "two-hit hypothesis," which implies that both alleles that code for a particular protein must be affected.  This is because if only one allele for the gene is damaged, the second can still produce the correct protein.  In other words, mutant tumor suppressors' alleles are usually recessive whereas mutant oncogene alleles are typically dominant.
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  History Alfred George Knudson,Jr. was an American physician and geneticist specializing in cancer genetics. Among his many contributions to the field was the formulation of the Knudson hypothesis in 1971, which explains the effects of mutation on carcinogenesis.
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  Fig. Illustration ofhow a normal cell is converted to a cancer cell, when an oncogene becomes activated
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   The two-hithypothesis was first proposed by A.G. Knudson for cases of retinoblastoma.  Knudson observed that the age of onset of retinoblastoma followed 2nd order kinetic
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  Functions  Tumor-suppressor genes,or more precisely, the proteins for which they code, either have a damping or repressive effect on the regulation of the cell cycle or promote apoptosis, and sometimes do both. The functions of tumor-suppressor proteins fall into several categories including the following: 1. Repression of genes that are essential for the continuing of the cell cycle. If these genes are not expressed, the cell cycle does not continue, effectively inhibiting cell division. 2. Coupling the cell cycle to DNA damage. As long as there is damaged DNA in the cell, it should not divide. If the damage can be repaired, the cell cycle can continue.
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  3. If thedamage cannot be repaired, the cell should initiate apoptosis (programmed cell death) 4. DNA repair proteins are usually classified as tumor suppressors as well, as mutations in their genes increase the risk of cancer, for example mutations in HNPCC, MEN1 and BRCA.
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  Examples  The firsttumor-suppressor protein discovered was the Retinoblastoma protein (pRb) in human retinoblastoma; however, recent evidence has also implicated pRb as a tumor-survival factor.  Another important tumor suppressor is the p53 tumor- suppressor protein encoded by the TP53 gene.  Homozygous loss of p53 is found in 65% of colon cancers, 30–50% of breast cancers, and 50% of lung cancers.  Mutated p53 is also involved in the pathophysiology of leukemias, lymphomas, sarcomas, and neurogenic tumors.  Abnormalities of the p53 gene can be inherited in Li- Fraumeni syndrome (LFS), which increases the risk of developing various types of cancers.
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  References  The cell-Geoffrey M. Cooper (Fifth Edition)  Google – www.google.com