publicado em 17/05/2012 às 13h21:00
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Reactivation of genes "switched off" by cancer kills tumor cells

Study results have potential for developing a new generation of therapies to eliminate cancer cells

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A survey conducted in the United States identified the epigenetic changes that are essential for the survival of cancer cells. The experimental study has demonstrated that tumor cells are reactivated die when the genes had been turned off by epigenetic disorder. The results are published in this week's edition of the journal Cancer Cell.

According to the Brazilian researcher Daniel Diniz de Carvalho, who participated in the American survey, the main objective is to contribute to the development of a new generation of epigenetic therapies. Epigenetic therapies are being used clinically, but they change the whole pattern of the DNA, activating not only the genes that prevent tumor survival, but also several others that should not be activated. Because they are nonspecific therapies are at high risk. In this study, we identified important targets for the future development of second generation, more efficient, epigenetic therapies.

All cells in the body have the same genetic information. What makes the distinction between them, allowing the formation of various tissues, is the fact that certain genes are turned on or off. This adjustment is made by epigenetic mechanisms, as DNA methylation and chromatin changes.

When this mechanism is distorted by an epigenetic modification, there may be various diseases, especially cancer. When this change takes the cell to become a tumor, it loses even more control of the regulatory mechanism. The cell then begins to accumulate other mutations that have no importance in the genesis of the tumor, he explained.

Distinguish important epigenetic changes - which guarantee the survival of the tumor - the changes caused by the very presence of the tumor is a major problem for science.

With new sequencing techniques available, we mapped all the genetic and epigenetic alterations. But as only analyzed the tumor cell at the end of the process, we do not know what changes are the cause and what are the consequences, said Carvalho.

Genes <b> key </ b>

Identify epigenetic changes essential for the survival of the tumor is critical to identify appropriate therapeutic targets, according to Carvalho.

A genetic mutation is a permanent change, but epigenetic changes are reversible and therefore are very interesting for potential therapies, he said.

To identify the essential epigenetic changes, the scientists analyzed a tumor cell with large amounts of aberrant methylation and gradually reduced the levels of enzymes that produce DNA methylation.

Reducing the availability of methylation, we put pressure on the methylation was only addressed to the DNA needed. At some point the cancer cell survived. After a certain level of reduction the cell did not survive and we knew then that the last methylated DNA were essential for the survival of the tumor, the researcher added.

Then, the scientists have mapped the genome and found had the main key genes. Using tumor samples from the International Cancer Genome Atlas consortium, found that fundamental genes were always active in tumor cells.

After reactivated these genes in cells, to make sure that it was important. Once the genes were reactivated, tumor cells died. In fact, the survival of the tumor is possible only when these genes are silenced, he said.

Although inactive, the key genes in tumor cells remain intact. According to Carvalho, the challenge now is figuring out how to reverse DNA methylation, reactivating these genes to kill the tumor.

A major objective of this research is to identify a mechanism for finding a specific target genes, enabling a second generation of epigenetic therapies. Another goal is to improve the results of nonspecific epigenetic therapies that enable many genes to the tumor cell to become immunogenic. We think we can improve these therapies combining them with immunotherapy, said.

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   Palavras-chave:   Cell cancer    Epigenetics    United States    DNA    UNB    University of Brasilia   
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