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    Paul K. Brindle, PhD

    Paul K. Brindle, PhD

    Genetic secrets hold promise for treating solid tumors

    A biochemical mechanism that cells use to cope with hypoxia (lack of oxygen) actually cooperates with a less well-known mechanism that helps increase the expression of those hypoxia-sensitive genes, according to investigators at St. Jude Children's Research Hospital.

    The two mechanisms each enable a transcription factor called hypoxia-inducible factor (HIF) to increase expression of genes that the cell uses to respond to the stress of hypoxia. Transcription factors bind to a site on the gene called the promoter and trigger the process that decodes the gene and makes the protein for which that gene codes. HIF binds to and activates many genes that contribute to the survival response of tumors; for example, genes that control biochemical reactions that don’t require oxygen to extract energy from glucose or genes needed to build new blood vessels that bring oxygen to hypoxic cells.

    The finding is important because it suggests that developing new therapies that interfere with both mechanisms instead of just one might enhance the efficacy of treatments designed for solid tumors that become hypoxic as they outgrow their oxygen supply, according to Paul Brindle, PhD, of the St. Jude department of Biochemistry. Brindle is senior author of a report on this work that appeared in November 16 issue of The EMBO Journal. Lawryn Kasper, PhD,  of St. Jude Biochemistry, is first author of the article and together with Fayçal Boussouar, PhD, did most of the work on this study.

    Other authors of the study are Troy Baudino, Michelle Biesen, John Cleveland, PhD, and Wu Xu, St. Jude Biochemistry; Kelli Boyd, DVM, PhD, ARC; and Jerold Rehg, DVM, of the St. Jude department of Pathology.

    St. Jude does both laboratory and clinical research in order to find cures for catastrophic diseases of children. Much of this research, especially in the laboratory, leads to discoveries of the basic workings of the body's cells. Therefore, some of our work has broader implications than childhood diseases and provides insights into adult diseases as well.


    Last update: January 2006