title: MMP-9 overexpression due to TIMP-1 and RECK underexpression is associated with prognosis in prostate cancer.
abstract: BACKGROUND
  Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9 and its specific inhibitors, TIMP-1 and RECK, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome in prostate cancer (PC).
  
  
  METHODS
  MMP-9, TIMP-1, and RECK expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue specimens collected from 79 patients with clinically localized PC submitted to radical prostatectomy (RP). Frozen benign prostatic tissue from another 10 men with prostate cancer, also submitted to RP, was analyzed to determine if the profile of gene expression was maintained. The control group consisted of 11 patients with benign prostate hyperplasia (BPH).
  
  
  RESULTS
  In the tumor samples, MMP-9 was overexpressed by 9.2 times, and TIMP-1 and RECK were underexpressed (0.75 and 0.80 times, respectively). Overexpression of MMP-9 was significantly related to PSA levels above 10 ng/mL (p=0.033). In addition, MMP-9 overexpression was related to biochemical recurrence, with a marginal statistical significance (p=0.089). MMP-9 was also overexpressed in benign tissues of patients with PC, as were TIMP-1 and RECK, in contrast to their underexpression in tumor samples.
  
  
  CONCLUSIONS
  Our results show that MMP-9 is overexpressed and its negative regulators are underexpressed in PC tissue, emphasizing a possible role of MMP-9 in the carcinogenesis process. Additionally, we noticed a relationship between MMP-9 overexpression and increased levels of PSA, an important prognostic factor. In benign tissue adjacent to tumors, the MMP-9 equilibrium is likely maintained because the expression of its negative regulators is preserved.
authors.affiliation: Laboratory of Medical Investigation (LIM55), Urology Department, University of Sao Paulo Medical School, Sao Paulo - Brazil. sasareis@gmail.com
authors.forename: Sabrina Thalita
authors.initials: ST
authors.lastname: Reis
authors.forename: José
authors.initials: J
authors.lastname: Pontes-Junior
authors.forename: Alberto Azoubel
authors.initials: AA
authors.lastname: Antunes
authors.forename: Juliana Moreira
authors.initials: JM
authors.lastname: de Sousa-Canavez
authors.forename: Marcos Francisco
authors.initials: MF
authors.lastname: Dall'Oglio
authors.forename: Carlo C
authors.initials: CC
authors.lastname: Passerotti
authors.forename: Daniel Kanda
authors.initials: DK
authors.lastname: Abe
authors.forename: Alexandre
authors.initials: A
authors.lastname: Crippa
authors.forename: Jose Arnaldo Shiomi
authors.initials: JA
authors.lastname: da Cruz
authors.forename: Luciana M S
authors.initials: LM
authors.lastname: Timoszczuk
authors.forename: Miguel
authors.initials: M
authors.lastname: Srougi
authors.forename: Kátia R M
authors.initials: KR
authors.lastname: Leite
mesh_terms: D000328:Adult; D000368:Aged; D058851:GPI-Linked Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: D058851:GPI-Linked Proteins; C115460:RECK protein, human; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9