The AP-1 site and MMP gene regulation: What is all the fuss about?

Benbow, Ulrike; Brinckerhoff, Constance E.

doi:10.1016/s0945-053x(97)90026-3

Cited by 475 publications

(358 citation statements)

References 41 publications

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“…12 MMP-2 and -9 were thought to be the key matrix matalloproteinases involved in cancer cell invasion and metastases, since their overexpression could be induced by many factors such as cytokines, growth factors and oncogenes. [13][14][15][16][17] In the present study, we further demonstrated that MMP-9 levels in prostate tissues could also be an important MMP in cancer progression and metastasis. The activity of MMP-9 in metastatic prostate cancer tissues was about three-fold higher than that in BPH and about nine-fold higher than that in normal tissues.…”

Section: Discussionsupporting

confidence: 59%

Type IV collagenase (matrix metalloproteinase-2 and -9) in prostate cancer

Zhang

Shi

Feng

et al. 2004

Prostate Cancer Prostatic Dis

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Background: The type IV collagenases/gelatinases matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) play an important role in cancer invasion and metastasis. In the present study, we measured the expression of mRNAs and enzymatic activities of MMP-9 and -2 in prostate tissues and serum samples from men with or without prostate cancer. Methods: A total of 44 tissue samples (three from healthy volunteers, 21 from patients with benign prostate hyperplasia, 10 from patients with localized prostate cancer and 10 from patients with metastatic disease) and 71 serum samples were collected (20 from healthy volunteers, 26 from patients with benign prostatic hyperplasia, 10 from patients with localized cancer, 15 from patients with metastatic cancer). The level of mRNA for MMP-2 and -9 was determined by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The enzymatic activity of MMPs was determined by zymography. Results: Expression of MMP-9 mRNA was significantly higher in malignant than in nonmalignant prostate tissues (Po0.001), while no significant difference of MMP-2 expression was detected in different prostate tissues. Results of zymography showed that there was significant difference in the enzymatic activity of MMP-9, but not MMP-2, among normal prostate, BPH, localized and metastatic prostate cancer tissues, serum samples (Po0.05). The active form of MMP-2, with a molecular mass of 62 kDa, was detected in normal prostate, BPH and prostate cancer tissues, but not in the serum samples. Moreover, there was a significant difference in the ratio of the active form (62 kDa) and proform (72 kDa) of MMP-2 among normal, BPH and prostate cancer tissues. This ratio was further increased in metastatic prostate cancer tissues. Conclusion: The activity of MMP-9 and the ratio of active form/proform of MMP-2 are associated with the progression and metastasis of prostate cancer.

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Section: Discussionsupporting

confidence: 59%

Type IV collagenase (matrix metalloproteinase-2 and -9) in prostate cancer

Zhang

Shi

Feng

et al. 2004

Prostate Cancer Prostatic Dis

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“…Nevertheless, the need to validate the role of MMP-1s in cancer development and progression still remains (26)(27)(28). Interestingly, MMP-1 was reported as one of the first verified AP-1 target genes, and several other MMPs, including MMP3 and MMP9, have long been known to be regulated by AP-1 in a variety of cellular contexts (29,30). Our results clearly showed that HER2 overexpression can increase the binding activity of AP-1 to the AP-1 site within the MMP-1 promoter.…”

Section: Discussionsupporting

confidence: 54%

Matrix Metalloproteinase-1 Expression Can Be Upregulated through Mitogen-Activated Protein Kinase Pathway under the Influence of Human Epidermal Growth Factor Receptor 2 Synergized with Estrogen Receptor

Jung

Park

Jun

et al. 2010

Molecular Cancer Research

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In our previous work, Ets-1 upregulates human epidermal growth factor receptor 2 (HER2) induced matrix metalloproteinase 1 (MMP-1) expression. Based on the above knowledge and result, we hypothesized that estrogen receptor (ER) and its signaling pathway may affect MMP-1 expression under the influence of HER2. In addition, we investigated how the HER2 pathway cross-talk with the ER signaling pathway in genomic and nongenomic action of ER using reverse transcription-PCR, Western blot analysis, and ELISA assay. The results showed that ER-α expression increased MMP-1 expression under the presence of HER2. These upregulatory effects were mediated mainly by mitogen-activated protein kinase pathway and were reversed by downregulation of HER2 and/or ER. Activator protein DNA binding activity was involved in the MMP-1 expression. In summary, our results showed that ER can upregulate MMP-1 expression under the influence of HER2 in MCF-7 cells. In addition, this upregulatory effect was found to be mediated by mitogen-activated protein kinase pathway. MMP-1 might be an assigned target in interaction between ER and HER2.

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“…Differences among the MMP promoters have been described and include not only binding sites for different transcription factors but also variability in the number and arrangement of binding sites, which strongly increases the complexity of MMP regulation. 59 In summary, our data show that basal expression of the chemokine CXCL12 is increased in RASFs due to a defect in gene regulation by DNA methylation. In RA joints, accumulated CXCL12 produced by RASFs might lead to increased expression of MMPs, which mediate joint destruction.…”

Section: Dna Methylation Regulates the Expression Of Cxcl12 E Karouzamentioning

confidence: 69%

DNA methylation regulates the expression of CXCL12 in rheumatoid arthritis synovial fibroblasts

et al. 2011

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In the search for specific genes regulated by DNA methylation in rheumatoid arthritis (RA), we investigated the expression of CXCL12 in synovial fibroblasts (SFs) and the methylation status of its promoter and determined its contribution to the expression of matrix metalloproteinases (MMPs). DNA was isolated from SFs and methylation was analyzed by bisulfite sequencing and McrBC assay. CXCL12 protein was quantified by enzyme-linked immunosorbent assay before and after treatment with 5-azacytidine. RASFs were transfected with CXCR7-siRNA and stimulated with CXCL12. Expression of MMPs was analyzed by real-time PCR. Basal expression of CXCL12 was higher in RASFs than osteoarthritis (OA) SFs. 5-azacytidine demethylation increased the expression of CXCL12 and reduced the methylation of CpG nucleotides. A lower percentage of CpG methylation was found in the CXCL12 promoter of RASFs compared with OASFs. Overall, we observed a significant correlation in the mRNA expression and the CXCL12 promoter DNA methylation. Stimulation of RASFs with CXCL12 increased the expression of MMPs. CXCR7 but not CXCR4 was expressed and functional in SFs. We show here that RASFs produce more CXCL12 than OASFs due to promoter methylation changes and that stimulation with CXCL12 activates MMPs via CXCR7 in SFs. Thereby we describe an endogenously activated pathway in RASFs, which promotes joint destruction.

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The AP-1 site and MMP gene regulation: What is all the fuss about?

Cited by 475 publications

References 41 publications

Type IV collagenase (matrix metalloproteinase-2 and -9) in prostate cancer

Type IV collagenase (matrix metalloproteinase-2 and -9) in prostate cancer

Matrix Metalloproteinase-1 Expression Can Be Upregulated through Mitogen-Activated Protein Kinase Pathway under the Influence of Human Epidermal Growth Factor Receptor 2 Synergized with Estrogen Receptor

DNA methylation regulates the expression of CXCL12 in rheumatoid arthritis synovial fibroblasts

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