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Gene Amplification

In this very unusual process, the normal DNA replication process is seriously flawed. The result is that instead of making a single copy of a region of a chromosome, many copies are produced. This leads to the production of many copies of the genes that are located on that region of the chromosome. Sometimes, so many copies of the amplified region are produced that they can actually form their own small pseudo-chromosomes called double-minute chromosomes.

 

gene overproduction

 

The genes on each of the copies can be transcribed and translated, leading to an overproduction of the mRNA and protein corresponding to the amplified genes as shown below. The squiggly lines represent mRNA being produced via the transcription of each copy of the gene.

 

 

While this process is not seen in normal cells, it occurs quite often in cancer cells. If an oncogene is included in the amplified region, then the resulting overexpression of that gene can lead to deregulated cell growth. Examples of this include the amplification of the myc oncogene in a wide range of tumors and the amplification of the ErbB-2 or HER-2/neu oncogene in breast and ovarian cancers. In the case of the HER-2/neu oncogene, clinical treatments have been designed to target cells overexpressing the protein product.

Gene amplification also contributes to one of the biggest problems in cancer treatment: drug resistance. Drug resistant tumors can continue to grow and spread even in the presence of chemotherapy drugs. A gene commonly involved is called MDR for multiple drug resistance. The protein product of this gene acts as a pump located in the membrane of cells. It is capable of selectively ejecting molecules from the cell, including chemotherapy drugs. This removal renders the drugs ineffective.

This is discussed in more detail in the section on Drug Resistance. The amplification of different genes can render other chemotherapy drugs ineffective.

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