Accession Number : ADA437246


Title :   Endometase in Androgen-Repressed Human Prostate Cancer


Descriptive Note : Annual rept. 25 Feb 2004-25 Feb 2005


Corporate Author : FLORIDA STATE UNIV TALLAHASSEE


Personal Author(s) : Sang, Qing-Xiang A.


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA437246


Report Date : MAR 2005


Pagination or Media Count : 124


Abstract : Prostate cancer invasion and metastasis is the leading cause of patient death. We reported the discovery, cloning, and characterization of human matrix metalloproteinase-26 (MMP- 26), endometase. We have been testing three specific hypotheses: 1) The expression levels of MMP-26 is correlated with the metastatic potentials and the degrees of malignancy of human prostate cells; 2)MMP-26 has unique structure and enzymatic function; 3) MMP-26 enhances prostate cancer invasion by digesting extracellular matrix proteins and inactivating serine proteinase inhibitors, and specific inhibitors of MMP-26 block prostate cancer invasion. We report that levels of MMP-26 protein in human prostate carcinomas and high-grade prostate intraepithelial neoplasia from multiple patients were significantly higher than those in prostatitis, benign prostate hyperplasia, and normal prostate glandular tissues. Prostate cancer cells transfected with MMP-26 cDNA are more invasive and with an inactive mutant are less invasive than the parental cell lines. MMP-26 promoted prostate cancer invasion via activation of pro-gelatinase B/MMP-9. The endometase active site has an intermediate S1' pocket using synthetic MMP inhibitors. Some new synthetic MMP inhibitors are stable in cell culture media and can block the invasion of prostate cancer cells. Papers published by Sang lab are attached.


Descriptors :   *ANDROGENS , *PROSTATE CANCER , TISSUES(BIOLOGY) , ENZYMES , MUTATIONS , CLONES , GENETIC ENGINEERING , METASTASIS , CELLS(BIOLOGY) , CULTURES(BIOLOGY) , PROSTATE GLAND , PEPTIDE HYDROLASES , SERINE.


Subject Categories : BIOCHEMISRTY
      MEDICINE AND MEDICAL RESEARCH


Distribution Statement : APPROVED FOR PUBLIC RELEASE