MMP-9 overexpression due to TIMP-1 and RECK underexpression is associated with prognosis in prostate cancer
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Citações na Scopus
26
Tipo de produção
article
Data de publicação
2011
Título da Revista
ISSN da Revista
Título do Volume
Editora
WICHTIG EDITORE
Autores
Citação
INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS, v.26, n.4, p.255-261, 2011
Resumo
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 prostatectorny (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. Conclusion: 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.
Palavras-chave
Diagnosis, Gene expression, Matrix metalloproteinase, Prognosis, Prostate cancer
Referências
- Cox G, 2000, LUNG CANCER-J IASLC, V27, P81, DOI 10.1016/S0169-5002(99)00096-3
- Singh RD, 2011, INT J BIOL MARKER, V26, P27, DOI 10.5301/JBM.2011.6359
- Cho NH, 2003, EUR UROL, V44, P560, DOI 10.1016/S0302-2838(03)00362-2
- Kodate M, 1997, PATHOL INT, V47, P461, DOI 10.1111/j.1440-1827.1997.tb04525.x
- Eissa S, 2007, EUR UROL, V52, P1388, DOI 10.1016/j.eururo.2007.04.006
- Jemal A, 2010, CA-CANCER J CLIN, V60, P277, DOI [10.3322/caac.20073, 10.1002/caac.20073]
- PYKE C, 1992, CANCER RES, V52, P1336
- Toi M, 1998, BREAST CANCER RES TR, V52, P113, DOI 10.1023/A:1006167202856
- Henriet P, 1999, APMIS, V107, P111
- Chang CK, 2008, J CELL MOL MED, V12, P2781, DOI 10.1111/j.1582-4934.2008.00215.x
- Simi L, 2004, LUNG CANCER-J IASLC, V45, P171, DOI 10.1016/j.lungcan.2004.01.014
- Hsu MC, 2006, J BIOL CHEM, V281, P4718, DOI 10.1074/jbc.M510937200
- Zhong WD, 2008, ONCOLOGY-BASEL, V75, P230, DOI 10.1159/000163852
- Heppner KJ, 1996, AM J PATHOL, V149, P273
- Nawrocki B, 1997, INT J CANCER, V72, P556, DOI 10.1002/(SICI)1097-0215(19970807)72:4<556::AID-IJC2>3.0.CO;2-P
- Liabakk NB, 1996, CANCER RES, V56, P190
- Sasahara RM, 1999, BIOCHEM BIOPH RES CO, V264, P668, DOI 10.1006/bbrc.1999.1552
- Takeuchi T, 2004, CLIN CANCER RES, V10, P5572, DOI 10.1158/1078-0432.CCR-03-0656
- Polette M, 2004, CRIT REV ONCOL HEMAT, V49, P179, DOI 10.1016/j.critrevonc.2003.10.008
- Lichtinghagen R, 2002, EUR UROL, V42, P398, DOI 10.1016/S0302-2838(02)00324-X
- Takahashi C, 1998, P NATL ACAD SCI USA, V95, P13221, DOI 10.1073/pnas.95.22.13221
- Zerbib M, 2008, UROLOGY, V72, P25, DOI 10.1016/j.urology.2008.10.005
- Nelson AR, 2000, J CLIN ONCOL, V18, P1135
- Oh J, 2001, CELL, V107, P789, DOI 10.1016/S0092-8674(01)00597-9
- Berger AP, 2003, PROSTATE, V57, P93, DOI 10.1002/pros.10278
- Chang HC, 2004, CELL SIGNAL, V16, P675, DOI 10.1016/j.cellsig.2003.11.001
- Chen Wen-Tien, 1992, Current Opinion in Cell Biology, V4, P802, DOI 10.1016/0955-0674(92)90103-J
- Festuccia C, 2000, INT J CANCER, V85, P407, DOI 10.1002/(SICI)1097-0215(20000201)85:3<407::AID-IJC18>3.0.CO;2-8
- HAMDY FC, 1994, BRIT J CANCER, V69, P177, DOI 10.1038/bjc.1994.30