Accession Number : ADA430267


Title :   Protease Profiling in Prostate Cancer


Descriptive Note : Final rept. 1 May 2001-30 Apr 2004


Corporate Author : BURNHAM INST LA JOLLA CA


Personal Author(s) : Smith, Jeffrey W.


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA430267


Report Date : MAY 2004


Pagination or Media Count : 20


Abstract : Prostate cancer (PCa) is a leading cause of death in men in the United States (1). If detected early when the tumor is still confined to the prostate, there are a number of treatment regimens that lead to good prognosis. However, if the tumor escapes the prostate prior to diagnosis, patient prognosis is poor. The objective of the proposed study was to identify serine hydrolases that are aberrantly regulated in PCa and that contribute to progression of the disease. To accomplish this objective we undertook a unique approach called activity. based protein profiling. In this method, a chemical probe composed of a "warhead" and a detection reagent are used to covalently tag the active site of an enzyme. Using this strategy we have identified a number of novel serine hydrolases that are expressed in prostate cancer. Of special importance is an enzyme called fatty acid synthase, which contains a serine hydrolase domain. We identified a lead inhibitor of this domain of fatty acid synthase, called Orlistat, which is a drug approved for treating obesity. Our work also shows that Orlistat can slow the growth of prostate tumors in mouse models of human PCa.


Descriptors :   *GROWTH(PHYSIOLOGY) , *PROSTATE GLAND , *PEPTIDE HYDROLASES , *PROSTATE CANCER , DETECTION , CHEMICALS , ENZYMES , DISEASES , NEOPLASMS , PATIENTS , SYNTHASES , DEATH , SERINE , FATTY ACIDS , OBESITY.


Subject Categories : BIOCHEMISRTY
      MEDICINE AND MEDICAL RESEARCH


Distribution Statement : APPROVED FOR PUBLIC RELEASE