RECK is not an independent prognostic marker for breast cancer (original) (raw)
Related papers
Journal of Gastroenterology, 2011
Background Reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) has been implicated in the attenuation of tumor metastasis by negatively regulating metalloproteinase (MMP) levels. RECK gene expression is downregulated in many solid tumors, with this downregulation being associated with poor prognosis. This study evaluated the role of RECK in cholangiocarcinoma (CCA). Methods The expression of RECK, MMP-2, and MMP-9 in paraffin sections of hamster and human CCA specimens was analyzed by immunohistochemistry. Functional analysis of RECK was performed in RECK small interfering (si) RNA knockdown CCA cell lines. The effect of aspirin on RECK status and function was evaluated using Western blotting, gelatin zymography, invasion and proliferation assays, and PhosphoELISArray analysis of Ras downstream mediators. Results Hamster tissues showed high RECK expression in hyperplastic biliary duct epithelia, low RECK expression in precancerous lesions, and no RECK expression in CCA. In human specimens, RECK was highly expressed in normal biliary cells, whereas intrahepatic CCA showed low levels of expression. Downregulation of RECK was correlated with tumor metastasis (P < 0.01) and shorter patient survival (P < 0.02). RECK expression levels were inversely correlated with MMP-2 and MMP-9 expression (P < 0.05). SiRNA RECK-depleted M139 CCA cells exhibited increased MMP-2/-9 gelatinase activities and invasiveness. Aspirin (500 μM) demonstrated myriad effects in human CCA cell lines, including growth suppression, reduced phosphorylation of Akt/Erk/c-Jun, elevation of RECK expression, inhibition of MMP-2/MMP-9 activity, and enhanced invasiveness. Conclusions RECK functions as a metastasis suppressor in CCA; upregulation of RECK expression could provide a potential therapy to improve the prognosis of this type of cancer.
Matrix Metalloproteinase Inhibitor RECK Expression in Canine Tumors
Journal of Veterinary Medical Science, 2005
Matrix metalloproteinases (MMPs) selectively degrade the extracellular matrix, and they have been reported to play an important role in tumor invasion, metastasis and angiogenesis. These enzymes are closely related to tumor malignancy and patient survival time. Recently, reversion-inducing cysteine-rich protein with Kazal motifs (RECK) gene was identified as an endogenous membraneanchored MMP inhibitor. The down-regulation of RECK has been implicated in tumor progression. In this study, the expression levels of the RECK messenger ribonucleic acid (mRNA) in various spontaneously developed canine tumors were investigated by using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), and the correlation between RECK and clinicopathological factors, as well as MMP-9 expression were analyzed. The median age of 36 dogs investigated in this study was 9 years old (range, 1-15 years old). Quantitative RT-PCR could detect low levels of expression of RECK mRNA in the tumor samples. The expression levels of RECK mRNA in some tumor tissue samples were significantly lower than those in normal tissue samples. No significant associations of RECK with clinicopathological factors were observed. Using the Mann-Whitney U test, the expression level of the MMP-9 mRNA was observed to be significantly correlated to RECK expression (p<0.05).
Evaluation of RECK mRNA and RECK protein in tissue and serum of breast cancer patients
Gene Reports, 2018
Background: breast cancer (BC) is the most notorious females' cancer with high morbidity and mortality. RECK is an inhibitor of matrix metalloproteinase, and cellular invasion. Although high expression levels of RECK has been correlated with a better clinical outcome for several tumor types, its clinical significance for BC, remains unclear. The present study aimed to investigate the expression of RECK gene in BC patients to evaluate its clinical utility. Methods: The current study included 120 breast tissue and serum specimens from patients with BC, and control females. The two groups were matched for age, menopausal status, and the use of hormonal therapy or oral contraceptive pills (OCP). The expression of RECK mRNA, and protein was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and enzyme linked immunosorbent assay (ELISA), respectively. Results: The expression of both RECK mRNA and protein was lower in tissues, and sera samples obtained from BC patients than the control group. The tissue levels of RECK mRNA and RECK protein were high in premenopausal and OCP users. The sensitivity of RECK mRNA in tissue and serum was100%. Both mRNA and protein levels of RECK in serum were positively correlated with their levels in breast tissue. Conclusion: These findings illustrate the clinical value of RECK as a molecular marker for BC, and the feasibility of liquid biopsies to determine RECK expression.
Cancer Letters, 2006
mRNA, and latent and active levels MMP-2 and -9 were higher in tumor tissue compared to normal tissue from 63 patients with colorectal cancer, whereas RECK and EMMPRIN levels were lower. Correlations between mRNA, latent, and active MMP were particular high for MMP-2 in tumor tissue (R s Z0.6-0.8, P!0.001). For active MMP-2, but not for MMP-9, a significant negative partial correlation (R p ZK0.440, P!0.001) for RECK was found in tumor tissue, which was confirmed by linear regression analysis. In exploratory survival analyses we found that in patients with localized disease the RECK level in normal or tumor tissue had a significant (PZ0.017) association with overall survival. q
RECK Negatively Regulates Matrix Metalloproteinase-9 Transcription
Cancer Research, 2009
RECK, a glycosylphosphatidylinositol-anchored glycoprotein, inhibits the enzymatic activities of some matrix metalloproteinases (MMP), thereby suppressing tumor cell metastasis; however, the detailed mechanism is still obscure. In this study, we compared the gene expression profiles between mock-and RECK-transfected HT1080 cells and showed that RECK decreases MMP-9 mRNA levels but not other MMP mRNA levels. Moreover, treatment with RECK-specific siRNA increased MMP-9 mRNA in RECK-expressing cells. The promoter assay showed that MMP-9 promoter activity was suppressed by RECK and that RECK-mediated suppression of MMP-9 promoter activity requires 12-O-tetradecanoylphorbol-13acetate-responsive element (TRE) and KB sites. Moreover, the binding ability of Fra-1 and c-Jun to TRE within the MMP-9 promoter region was suppressed by RECK. Thus, these results show that RECK is a negative regulator of MMP-9 transcription.
Molecular Cloning of Canine Membrane-Anchored Inhibitor of Matrix Metalloproteinase, RECK
Journal of Veterinary Medical Science, 2005
The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) gene is one of the endogenous matrix metalloproteinase (MMP) inhibitors. It was reported that decreased RECK expression closely correlated with tumor malignancy. We determined the cDNA sequence of the canine RECK gene. The cDNA sequence and deduced amino acid of canine RECK were 2,913 bases and 971 residues, respectively. The predicted amino acid sequence of the protein showed 95.5% and 91.9% homology with human and mouse RECK, respectively. RECK mRNA expression was analyzed in various canine tissues and tumor cell lines by quantitative RT-PCR. The highest RECK expression was detected in lung and testis. In comparison with the tissues, a remarkably low expression level was detected in tumor cell lines. In addition, the RECK gene was transfected in the canine transitional cell carcinoma, and its influence on cell proliferation, migration, and invasion was analyzed. The transfected RECK gene suppressed only canine tumor invasion. These results showed that RECK might play an important role in tumor malignancy in dogs as well as in other mammalians.
Annals of Oncology, 2008
Traditionally, matrix metalloproteinases (MMPs) have been implicated in cancer invasion and metastasis. Because of their role in these processes, several MMPs have been investigated for potential prognostic value as well as targets for antimetastatic therapy. In this investigation, we used a publically available database to relate messenger RNA expression levels for 17 different MMPs to tumor characteristics and outcome in patients with breast cancer. Of the MMPs investigated, only MMP-1 was significantly increased in tumors >2 cm in size compared with those £2 cm while MMP-1,-9,-12 and-15 were significantly elevated in high-grade compared with low-grade tumors. Only MMP-10 was higher in lymph node-positive compared with lymph node-negative cancers. Using univariate analysis, high expressions of MMP-1,-9,-12,-14 and-15 were associated with poor overall survival. Of these five, only MMP-14 predicted outcome independent of tumor size, tumor grade and lymph node status. None of the MMPs investigated were associated with good outcome. We conclude that only a minority of MMPs, i.e. MMP-1,-9,-12,-14 and-15, are associated with adverse outcome in patients with breast cancer. These MMPs are likely to be involved in mediating breast cancer progression and may thus be good targets for designing specific MMP inhibitors for the treatment of breast cancer.
Clinical Cancer Research, 2004
Purpose: In the present study, we investigated the expression and prognostic value of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer as well as their relation to transcription factor activator protein (AP)-2 and HER2 oncogene. The role of invasion and metastasis-promoting MMPs and their potential regulators, AP-2 and HER2, is currently still unclear in breast cancer. Experimental Design: MMP-2 and MMP-9 expressions were analyzed immunohistochemically in a large prospective series of 421 breast cancer patients diagnosed and treated between 1990 and 1995 at Kuopio University Hospital (Kuopio, Finland). The relation of MMP-2 and MMP-9 expressions to AP-2, HER2, clinicopathological data, and survival was investigated. Results: Both MMP-2 and MMP-9 were expressed in the cytoplasm of malignant and stromal cells. High expression of MMPs in carcinoma cells was related to small tumors (T1, stage I), whereas positive stromal expression of MMPs was associated with aggressive facto...