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gene amplification

Gene amplification involves the production of multiple copies of a gene through repeated copying of the gene.

Amplification is distinct from duplication, which is precise genome doubling preparatory to cell division, and from endoreduplication, which leads to endopolyploidy. When many copies of the amplified region are produced, they can form their own small pseudo-chromosomes called 'double-minute chromosomes'.

Gene amplification results from dysfunction in malignant cell lines. However, some organisms have evolved mechanisms for gene amplification in order to provide needed gene products in large quantities. Such functional mechanisms include:
a. The elaboration of small "extrachromosomal" units that replicate to high copy number (rDNA);
b. Tandem gene duplications (DHFR);
c. Localized endoreduplication of chorion genes.

Different organisms employ different mechanisms. Sometimes, as for double-minute chromosomes and human secretin receptor gene* (HSR), more than one mechanisms is employed within an organism.

Some mutants in developmentally expressed genes of plants result from heritable gene amplification. Gene amplification can be regulated developmentally, temporally, or environmentally.

Neoplastic cells can amplify, or copy, DNA segments in response to cellular signals or environmental events. When an oncogene is included in the amplified region, then the resulting overexpression of the oncogene gene leads to deregulated cell growth. Examples include amplification of the MYC oncogene in a wide range of tumors, and amplification of the ErbB-2 or HER-2/neu oncogene in breast and ovarian cancers. Clinical treatments have been designed to target cells overexpressing the HER-2/neu oncogene protein product.

Resistance of cancer cells to chemotherapeutic agents is linked to amplification of the gene that prevents absorption of the drug by the cell. A gene called MDR, for 'multiple drug resistance', is commonly involved. The protein product of the MDR gene acts as a membrane pump that selectively ejects molecules, including chemotherapy agents, rendering the drugs ineffective.

* the human secretin receptor (hSR) is an important glycoprotein receptor involved in regulation of the secretion of pancreatic bicarbonate, water, and electrolytes.


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Blogger Da Baka said...

so, what are the mechanisms of gene amplification?

6:42 AM  

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