Tumor Suppression Gene

Tumor suppression gene also known as antioncogene refers to genes regulating cell growth. This gene protects the cell from been cancerous and when it mutates causing reduction or loss of function, the cells then progress to cancer. This occurs when other genetic changes are present as well. Loss of the tumor suppressor gene is more important than oncogene/proto-oncogene activation in the formation of different kinds of human cancerous cells. There are different kinds of tumor suppressor genes and they include the following:

• Gatekeeper genes
• Caretaker genes
• Landscaper genes

As medicine continues to evolve, classification genes also evolve and adapt from fields such as genetics, epigenetic and molecular biology.

Unlike the case of oncogenes, tumor suppressor genes follow “two-hit hypothesis”. This implies both alleles coding for a certain protein must first be affected before any effect is noted. This is attributed to the fact that just one allele for that gene gets damaged while the second still produces the appropriate protein. In other terms, this means distorted tumor suppressor alleles are recessive while mutant oncogene alleles are dominant.

A.G Knudson was the first one to make the proposal of two-hit analysis. He made the observation that onset of retinoblastoma follows the second order kinetics which implied that 2 self-determining genetic events were a necessity. He also made the recognition that it was consistent with recessive mutation which involved one gene but required biallelic mutation. In contrast though, oncogene mutations involve single allele since they are the gain of mutation functions.

There however exist exceptions to the rule of “two-hit’ for tumor suppressors like particular mutations in p53 gene product. Such mutations are known to function as “dominant negative” which means if there is a p53 mutated protein, it prevents the functioning of normal protein from an allele that is un-mutated. Other suppressor genes that are also an exception to the “two hit” rule include those exhibiting haploinsufficiency such as:

• NF1 in neurofibroma and
• PTCH in medulloblastoma.

A good example in this case is p27Kip 1 cell inhibitor cycle in which a single allele mutation leads to an increase in the susceptibility of carcinogen.  Tumor suppressor genes functions fall into different categories some of which include:

• Gene suppression which is important for continuation of cell cycle. When the genes aren’t expressed, then there is no continuation of the cell cycle hence cell division is inhibited
• Coupling of cell cycle to damage of DNA. If there isn’t damaged DNA then the cell shouldn’t divide. In cases where the damage is repairable, the cycle of the cell continues
• When the damage isn’t repairable, the cell initiates apoptosis and gets rid of the threat posed for the organisms good.
• Proteins involved in division of cells prevents tumor cells from dispersing, block contact inhibition loss and also inhibit metastasis

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References

http://en.wikipedia.org/wiki/Tumor_suppressor_gene

http://www.medicinenet.com/script/main/art.asp?articlekey=11940

http://lungcancer.about.com/od/glossary/g/tumorsuppressor.htm