NEW YORK (Reuters Health) - Using a chemical genetic test to screen for compounds that inhibit the nuclear export of a certain transcription factor may be useful in identifying new anti-cancer agents, a recent report suggests. Researchers have identified a transcription factor that is a downstream target of the PI3K/Akt pathway.
In a study reported in the December issue of Cancer Cell, Dr. Pamela A. Silver, from Harvard Medical School in Boston, and colleagues looked for chemicals that block the nuclear export of the factor, FOXO1a.
Previous reports have shown that the PI3K/Akt pathway is constitutively activated in a number of malignancies, including prostate cancer, melanoma, and renal cell carcinoma.
This aberrant activation results in FOXO1a being sent to the cytoplasm. Preventing FOXO1a from leaving the nucleus has been shown to reverse the tumorigenicity of cancer-prone cells.
The researchers identified several compounds that inhibited FOXO1a export and were able to determine the structure-function relationships involved.
“Our data suggests that this approach can lead to the identification of novel anti-cancer therapeutics,” Dr. Silver said in a statement. “In fact, some of the compounds identified with our method are FDA-approved drugs.”
Cancer Cell 2003;December:463-476.
MeSH Headings:Phosphotransferases: Phosphotransferases (Alcohol Group Acceptor): 1-Phosphatidylinositol 3-KinaseCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
