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GENE OR PATHWAY OF THE MONTH Robert L. Keith, MD,*† and Mark W. Geraci, MD† (J Thorac Oncol. 2006;1: 503–505) well-described membrane receptor (IP), and the second is at the nuclear membrane via the peroxisome-proliferator acti- vated receptors (PPARs). The IP is a single canonical cell rostacyclin is a naturally occurring eicosanoid that pos- membrane-specific seven-transmembrane domain G protein- Psesses anti-inflammatory and anti-metastatic properties coupled receptor that has been cloned and characterized, and has a suppressive role in tumor growth. Prostacyclin with ligand binding resulting in G protein activation and synthase (PGIS) is the final committed enzymatic step in the stimulation of adenyl cyclase (thereby increasing intracellular pathway of PGI production, occurring at a branch point cAMP). PPARs are members of the nuclear hormone recep- where substrate can be directed toward either PGI , throm- tor superfamily that act as ligand-activated transcription fac- boxane A (TxA ), or prostaglandin E (PGE ) (Figure 1). tors. Three isoforms have been identified: PPAR, , and 2 2 2 2 Eicosanoid production and balance is proving pivotal in lung –-all of which bind to specific DNA sequences as het- tumorigenesis. erodimers with the retinoic acid X-receptors and regulate gene transcription. PPAR expression
Journal of Thoracic Oncology – Wolters Kluwer Health
Published: Jul 1, 2006
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