Accession Number : ADB258930


Title :   Novel Fatty Acid Lipoxygenases in the Development of Human and Murine Prostate Cancer


Descriptive Note : Annual rept. 1 Oct 1998-30 Sep 1999


Corporate Author : VANDERBILT UNIV NASHVILLE TN SCHOOL OFMEDICINE


Personal Author(s) : Shappell, Scott


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/b258930.pdf


Report Date : Oct 1999


Pagination or Media Count : 42


Abstract : Changes in arachidonic acid (AA) metabolism may be crucial in development or progression of prostate adenocarcinoma (Pca). By immunohistochemistry, western blots, Northern blots, and enzyme assays, we have detected the uniform expression of a novel lipoxygenase, 15-LOX-2, in benign prostate. 15-LOX-2 and 15-HETE formation are substantially reduced or lost in the vast majority of Pca. In contrast to uniform 15-LOX-2 immunostaining in benign glands, tumors were focally (25 %) and completely 15- LOX-2 negative in 59/97 (61 %) and 41/97 (42 %), respectively. In paired tissues from the same patients, 15-HETE formation and 15-LOX-2 mRNA were reduced in tumor vs. benign in 12/14 and 10/11, respectively. In contrast, significant changes in 5-HETE and 12-HETE formation have not been detected. Increased COX-2 mRNA was detected in 3/7 tumors vs. benign. 15-HETE may be a ligand for peroxisome proliferator activated receptors (PPARs), particularly PPARgamma. By RT-PCR, we have detected mRNA for PPARalpha, beta, and gamma in 18/18 benign and in 9/9 tumor specimens. 15-HETE induced PPAR gamma- dependent transcription in Pca cell lines. 15-HETE/ PPAR gamma signaling effects on cell proliferation and differentiation are being examined.


Descriptors :   *PROSTATE GLAND , *PROSTATE CANCER , ACTIVATION , TISSUES(BIOLOGY) , HUMANS , ENZYMES , NEOPLASMS , METABOLISM , GAMMA RAYS , CELLS(BIOLOGY) , ASSAYING , RECEPTOR SITES(PHYSIOLOGY) , GROWTH(PHYSIOLOGY) , GLANDS , IMMUNOCHEMISTRY , FATTY ACIDS , HISTOCHEMISTRY


Subject Categories : Biochemistry
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE