Other Free Encyclopedias » Medicine Encyclopedia » Genetics in Medicine - Part 3 » Oncogenes - Early Oncogene Research, Rna Tumor Viruses And Proto-oncogenes, Proto-oncogene Activation Without Retroviruses

Oncogenes - Tumor Suppressor Genes

chromosome copies cancer cells dna

In 1983 Raymond White and Webster Cavanee, using a technique called chromosome mapping, learned that a loss of a small segment of human chromosome 13 was a recurring feature in retinoblastoma, a rare childhood cancer of the retina that can run in families. In this deleted region they discovered a gene called RB (for retinoblastoma), both copies of which are inactivated either by DNA deletion or by a mutation within the gene that destroys its function. Such inactivation of both copies of the RB gene occurs in about 40 percent of human cancers. The product of the normal RB gene functions as a brake to cell division, so that loss of this brake can lead to unregulated cell growth.

Another gene associated with cancer when both copies are affected by mutation is the p53 gene, which acts as a "guardian" of the genome. Normally, this gene product induces a cell suicide program called apoptosis in cells with damaged DNA. Loss of p53 activity allows cells with damaged DNA to grow and pass DNA mutations to their daughter cells. A third type of gene that plays a role in cancer when it is inactivated is NF1. This gene encodes a protein that turns off the Ras growth signal mentioned above. In this case, loss of NF1 function is another way that the Ras signal can be left constantly on.

Since the discovery of RB, researchers have identified several additional genes in which both copies are inactivated due to mutation or chromosomal deletion. These genes normally block cell growth; hence they are called tumor suppressor genes. Since both copies of these genes need to be inactivated in order to release cancer cells from growth inhibition, tumor suppressor genes act recessively. This contrasts to the oncogenes described above, where only one copy needs to be activated in order to promote cancer. Oncogenes, therefore, act in a dominant fashion.

Oncogenes - Multiple Genetic "hits" [next] [back] Oncogenes - Short-circuiting Normal Cell Growth Mechanisms

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