Influence of MMP-2 and MMP-9 promoter polymorphisms on gene expression and clinical outcome of non-small cell lung cancer

Rollin, Jérôme; Régina, Sandra; Vourc’h, Patrick; Iochmann, Sophie; Bléchet, Claire; Reverdiau, Pascale; Gruel, Yves

doi:10.1016/j.lungcan.2006.11.021

Cited by 91 publications

(106 citation statements)

References 21 publications

(55 reference statements)

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“…Pardo and colleagues (40) reported high gene expression of MMP-2 in type II alveolar epithelial cells (e.g., A549 cells). In addition, MMP-2 and MMP-9 have been associated with increased tumor spread and poor prognosis in lung cancer (7,8). Furthermore, previous studies have shown a significant prognostic value for MMP-2 in NSCLC (41).…”

Section: Discussionmentioning

confidence: 94%

“…Indeed, expression of MMP-2 and MMP-9 is associated with high metastasis potential in several human carcinomas (6). In addition, MMP-2/9 upregulation in NSCLC is significantly associated with poor clinical improvement of patients (7,8). MMPs are primarily regulated at the transcriptional level through activation protein-1 (AP-1) or NF-kB (9).…”

Section: Introductionmentioning

confidence: 99%

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Rho Guanine Nucleotide Exchange Factor 5 Increases Lung Cancer Cell Tumorigenesis via MMP-2 and Cyclin D1 Upregulation

Yang

et al. 2015

Molecular Cancer Therapeutics

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We sought to elucidate the role of Rho guanine nucleotide exchange factor 5 (ARHGEF5) in tumorigenesis of lung adenocarcinoma cells. ARHGEF5 protein levels were assessed in 91 human lung adenocarcinoma specimens, and A549 and NCI-H1650 cells, by IHC and Western blotting. In addition, ARHGEF5 mRNA expression was evaluated by quantitative reverse transcriptase-PCR. Furthermore, ARHGEF5 long and short isoform coexpression was detected by immunofluorescence. Finally, flow cytometry; CCK8 and wound-healing assays; cell invasion, migration and adhesion; and xenografts were used to evaluate the biologic significance of ARHGEF5. ARHGEF5 was significantly increased in lung adenocarcinoma tissues and cell lines. Interestingly, ARHGEF5 levels were significantly associated with tumor grade and pathologic stage, but not age, gender, T stage, or lymph node metastasis status. ARHGEF5 knockdown by RNAi resulted in dramatically reduced proliferation, adhesion, invasion, and migratory capability of A549 and NCI-H1650 cells. Likewise, protein levels of p-Src, p-Akt, and NF-kB were significantly decreased after ARHGEF5 knockdown. In parallel, increased S-phase population and MMP-2/cyclin D1 expression were observed in the cancer cells, which were not apoptotic. In addition, ARHGEF5 knockdown A549 and NCI-H1650 cells injected s.c. and i.v. into nude mice exhibited decreased xenograft volume and overtly reduced metastasis. Conversely, ARH-GEF5 overexpression in A549 and NCI-H1650 cells increased their tumorigenicity in vitro. ARHGEF5 acts as a proto-oncogene in human lung adenocarcinoma cell tumorigenesis.

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Rho Guanine Nucleotide Exchange Factor 5 Increases Lung Cancer Cell Tumorigenesis via MMP-2 and Cyclin D1 Upregulation

Yang

et al. 2015

Molecular Cancer Therapeutics

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“…Previous studies also reported that the -634 G/C polymorphism was associated with the clinical outcome of colorectal cancer and non-small cell lung cancer (Rollin et al, 2007;Langers et al, 2012). One previous meta-analysis found that overexpression of MMP-9 is associated with a poor prognosis for ESCC (Zeng et al, 2013).…”

Section: Discussionmentioning

confidence: 95%

Matrix metalloproteinase variants associated with risk and clinical outcome of esophageal cancer

Zhang

2015

Genet. Mol. Res.

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ABSTRACT. We conducted a case-control study to investigate the role of matrix metalloproteinase (MMP) 2, MMP3, and MMP9 single nucleotide polymorphisms on susceptibility to esophageal squamous cell carcinoma (ESCC) in a Chinese population, and their association with environmental factors. A total of 226 patients with ESCC, and 226 age-and gender-matched healthy controls were enrolled in this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was carried out on MMP2 -1306 C>T (rs243865), MMP3 -1171 5A>6A (rs3025058), and MMP9 -1562 C>T (rs3918242) genotypes. Unconditional regression analysis showed that individuals carrying the MMP2 -1306 TT genotype had a decreased incidence of ESCC compared to those with the CC genotype [odds ratio (OR) = 0.32; 95% confidence interval (CI), 0.10-0.89, P value = 0.02]. Moreover, MMP9 -1562 CC carriers were associated with an increased ESCC risk compared to those with the TT genotype (OR = 2.71; 95%CI, 1.04-7.87, P value = 0.02). In the Cox proportional hazards model, after adjusting for potential confounding factors, patients carrying the MMP9 -1562 CC genotype had a significantly increased risk of death from ESCC (hazard ratio = 2.97; 95%CI, 1.25-6.87, P value = 0.005). 4617Matrix metalloproteinases and esophageal cancer ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 4616-4624 (2015) In conclusion, this study showed that the MMP2 -1306 TT and MMP9 -1562 CC genotypes were associated with increased ESCC, and patients carrying the MMP9 -1562 CC genotype had a significantly increased risk of death from ESCC.

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“…The expression of TFPI-2 in tumors is inversely related to an increasing degree of malignancy, which may suggest that TFPI-2 can inhibit growth of neoplasms. TFPI-2 is an inhibitor of MMPs (matrix metalloproteinases) which can promote invasiveness of tumor through matrix degradation (14). The levels of TFPI-2 were very low or undetectable in many tumor cells but markedly upregulated in normal cells.…”

Section: Discussionmentioning

confidence: 99%

EGCG inhibits growth and induces apoptosis in renal cell carcinoma through TFPI-2 overexpression

Ding¹

2009

Oncol Rep

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Abstract. EGCG (epigallocatechin gallate), the major catechin found in green tea, has been shown to inhibit proliferation and induce apoptosis in many tumors. EGCG can inhibit DNMT (DNA methyltransferase) activity, and cause CpG demethylation and reactivation of methylation-silenced genes. Tissue factor pathway inhibitor-2 (TFPI-2), a member of the Kunitz-type serine proteinase inhibitor family, is inversely related to an increasing degree of malignancy. Our previous study showed that the expression of TFPI-2 and invasiveness of renal cell carcinoma had a negative correlation. Overexpression of TFPI-2 may induce tumor cell apoptosis in renal cell carcinoma. Lower expression of TFPI-2 in renal cell carcinoma was partly due to hypermethylation of the gene promoter. Herein, using MTT and flow cytometry, we demonstrated that EGCG can inhibit growth and induces apoptosis in renal cell carcinoma cell line 786-0. In addition, Western blotting and real-time RT-PCR showed that EGCG can upregulate expression of TFPI-2. Before and after EGCG treatment, real-time methylation specific PCR could not detect methylation status of TFPI-2 gene promoter in cell line 786-0. In vivo invasiveness and metastasis test did not indicate any significant differences between control and treatment group. Our results suggest that EGCG inhibits growth and induces apoptosis in renal cell carcinoma through TFPI-2 overexpression. This is the first report showing that EGCG is likely to be an effective agent for renal cell carcinoma.

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Influence of MMP-2 and MMP-9 promoter polymorphisms on gene expression and clinical outcome of non-small cell lung cancer

Cited by 91 publications

References 21 publications

Rho Guanine Nucleotide Exchange Factor 5 Increases Lung Cancer Cell Tumorigenesis via MMP-2 and Cyclin D1 Upregulation

Rho Guanine Nucleotide Exchange Factor 5 Increases Lung Cancer Cell Tumorigenesis via MMP-2 and Cyclin D1 Upregulation

Matrix metalloproteinase variants associated with risk and clinical outcome of esophageal cancer

EGCG inhibits growth and induces apoptosis in renal cell carcinoma through TFPI-2 overexpression

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