MMP-9 overexpression due to TIMP-1 and RECK underexpression is associated with prognosis in prostate cancer

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 rep...

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Published in:	The International journal of biological markers Vol. 26; no. 4; pp. 255 - 261
Main Authors:	THALITA REIS, Sabrina, PONTES-JUNIOR, Jose, SROUGI, Miguel, LEITE, Kátia R. M, AZOUBEL ANTUNES, Alberto, DE SOUSA-CANAVEZ, Juliana Moreira, FRANCISCO DALILOGLIO, Marcos, PASSEROTTI, Carlo C, KANDA ABE, Daniel, CRIPPA, Alexandre, SHIOMI DA CRUZ, Jose Arnaldo, TIMOSZCZUK, Luciana M. S
Format:	Journal Article
Language:	English
Published:	Milano Wichtig 01-10-2011
Subjects:	Adult Aged Analytical, structural and metabolic biochemistry Biological and medical sciences Fundamental and applied biological sciences. Psychology Gene Expression Profiling GPI-Linked Proteins - biosynthesis GPI-Linked Proteins - genetics GPI-Linked Proteins - metabolism Humans Investigative techniques, diagnostic techniques (general aspects) Male Matrix Metalloproteinase 9 - biosynthesis Matrix Metalloproteinase 9 - genetics Matrix Metalloproteinase 9 - metabolism Medical sciences Middle Aged Molecular biophysics Prognosis Real-Time Polymerase Chain Reaction Tissue Inhibitor of Metalloproteinase-1 - biosynthesis Tissue Inhibitor of Metalloproteinase-1 - genetics Tissue Inhibitor of Metalloproteinase-1 - metabolism Urinary system disease Prognosis Prostate disease Enzyme Tissue inhibitor metalloproteinase 1 Gene overexpression Metalloendopeptidases Biochemistry Malignant tumor Matrix metalloproteinase Gene expression Gelatinase B Peptidases Association Clinical biology Hydrolases Diagnosis Molecular biology Male genital diseases Prostate cancer Cancer
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Summary:	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). 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). 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0393-6155 1724-6008
DOI:	10.5301/JBM.2011.8831