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Mayo Clinic researchers find gene they believe is key to kidney cancer
Date:5/20/2010

3 regulates the expression of genes that are critical to cancer control in the kidney, and silencing it appears to be very important to the growth of kidney cancer and probably to others tumors, as well," he says. "No one could have guessed that would be the case in kidney cancer. This is a completely novel finding."

Adds first author Simon Cooper, Ph.D., a molecular biologist at Mayo Clinic, "This research is particularly exciting because GATA3 may be a good therapeutic target. Two classes of drugs known as histone methyltransferase inhibitors and histone deacetylase inhibitors are designed to remove the brakes that cancer puts on key genes, like GATA3, that are silenced during cancer."

The researchers say that GATA3 is silenced through methylation of the GATA3 gene, a chemical modification that commonly occurs in cancer due to a widespread genetic instability that activates methyltransferases and histone deacetylases (HDACs). This process occurs when methyltransferase and HDAC enzymes work together to attach or remove chemical groups from genes, effectively silencing them. The drugs used in this study work together to reverse methylation and deacetylation.

The HDAC inhibitor used in this study is currently being examined in clinical trials for other cancers. It is similar to HDAC inhibitors that are already approved by the Food and Drug Administration for use in cutaneous T cell lymphoma. Dr. Cooper says that data from this study proves that these drugs synergize to restore GATA3 function, but they still need to be tested in kidney cancer animal models to provide a rationale for proceeding to a cancer clinical trial in kidney cancer.

This study results from a 2003 discovery by Dr. Copland and his team that the loss of TRIII plays a critical role in kidney cancer cell growth. TRIII appears to be a tumor suppressor gene that blocks tumor growth. Although it is well known that the ligand, transforming growth factor beta (TGF-) bin
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Contact: Kevin Punsky
punsky.kevin@mayo.edu
904-953-0746
Mayo Clinic
Source:Eurekalert

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