Thursday, March 31, 2011

Tumor Suppressor Genes

Cancer is a deadly disease that affects many families today and I would bet money on the fact that everyone who reads this post probably knows someone who has some form of cancer. A large majority of cancers are caused when something called a tumor suppressor gene becomes mutated and changes the cell cycle, or the process of cell division. In its normal form, a tumor suppressor gene has the ability to regulate when cells are allowed to divide and multiply. When a cell divides, the genetic information in them, DNA, is replicated. During this replication process mistakes can be made and these mistakes are referred to as mutations. The problem of cancer occurs sometimes when there are mutations specific to the tumor suppressor gene. If this gene becomes mutated, the cell no passes mutant genetic information along to daughter cells. The daughter cells multiply exponentially and a cancer tumor forms.



Two types of tumor suppressor genes, Rb and p53, often become mutated and lead to different types of cancers. A mutation in Rb, which is located on the 13th chromosome in humans, leads to retinoblastoma, or cancer of the retina. The Rb gene is dominant so there must be two mutated alleles, or a mutated copy of Rb from both the mother and the father, in order for the cancer to persist. When a healthy, normal copy of Rb is present it interacts with the E2F protein which regulates the S phase, or the part of the cell cycle where DNA is replicated. E2F can only interact with Rb when Rb is phosphorylated, or has a phosphorus on the end of it. A mutated version of the Rb chain is not phosphorylated and can therefore not interact with the E2F protein. Retinoblastoma occurs because mutant Rb can not interact with E2F to stop the S phase of the cell cycle and cancerous cells can occur.



Mutations of another tumor suppressor, p53, causes 50% of cancers and these forms of cancers are the most aggressive and have the highest rates of fatalities. Cancers caused by p53 include bladder, breast, cervix, colon, lung, liver, prostate and skin cancers. The p53 gene is located on chromosome 17 and contains 393 amino acids. A mutation of just one amino acid leads to a loss of function of this gene. The p53 gene has the ability to stop the cell replication process when a mutated or potentially dangerous section of a copied gene is detected. After detecting this mutated section of gene the cell replication process is stopped and the p53 gene signals for cell suicide, or cell death to occur. By ending the cell division process of this specific cell, it essentially stops the growth of a cancerous tumor before it starts.



Mutations in both p53 and Rb have been attributed to the rampant growth of cancers in many patients. Tumor suppressor genes, when they are not mutated, do exactly what their name says; they suppress the growth of cancerous tumors. Another type of gene called a proto-oncogene allow a cell to continue dividing and gives it the "go" signal. When mutated, a proto-oncogene becomes and oncogene and the cell constantly divides without stopping. Therefore an oncogene and a tumor suppressor gene in a cell spells disaster because a mutated tumor suppressor gene allows mutated genetic information to persist in daughter cells and the oncogene continues cell division of cells with these mutated genes at an accelerated rate. Doctors study proto-oncogenes and tumor suppressor genes in order to better understand appropriate treatments they can give to cancer patients.

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