Matrix Metalloproteinase Gene Expression<sup>a</sup>

Matrisian, Lynn M.

doi:10.1111/j.1749-6632.1994.tb24723.x

Cited by 144 publications

(90 citation statements)

References 42 publications

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“…PEA3 proteins interact with an *10 base pair DNA sequence in the promoters of target genes resulting in regulation of transcription (Macleod et al, 1992;Seth et al, 1992;Wasylyk et al, 1993). Putative candidate PEA3 target genes include proteinases required for degradation of the extracellular matrix, including the serine urokinasetype plasminogen activator (Nerlov et al, 1992) and matrix metalloproteinases gelatinase B, interstitial collagenase, stromelysin-3 and matrilysin (Matrisian and Bowden, 1990;Matrisian, 1994;Higashino et al, 1995), which represent important factors contributing to cancer metastasis (Liotta et al, 1991;Kohn and Liotta, 1995). Many of these extracellular matrix degrading genes also contain AP1 sites in their promoters (Angel and Karin, 1991;Karin et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Cooperation between AP1 and PEA3 sites within the progression elevated gene-3 (PEG-3) promoter regulate basal and differential expression of PEG-3 during progression of the oncogenic phenotype in transformed rat embryo cells

Shi

Fisher

2000

Oncogene

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Cancer is a progressive disease in which a tumor cell temporally develops qualitatively new transformation related phenotypes or a further elaboration of existing transformation associated properties. Subtraction hybridization identi®ed a novel gene associated with transformation progression in mutant adenovirus type 5, H5ts125, transformed rat embryo cells, progression elevated gene-3 (PEG-3). To de®ne the mechanism by which expression of PEG-3 is enhanced as a function of cancer progression a 5'-¯anking promoter region of *2.0-kb, PEG-Prom, was isolated, cloned and characterized. The full-length and various mutated regions of the PEG-Prom were linked to a luciferase reporter construct and evaluated for promoter activity during cancer progression. These assays demonstrate a requirement for AP1 and PEA3 sites adjacent to the TATA box region of PEG-3 in mediating basal promoter activity and the enhanced expression of PEG-3 in progressed H5-ts125-transformed rat embryo cells. An involvement of AP1 and PEA3 in PEG-3 regulation was also con®rmed by electrophoretic mobility shift assays (EMSA) and transfection studies with cJun and PEA3 expression vectors. Our ®ndings document the importance of both AP1 and PEA3 transcription factors in mediating basal and elevated expression of PEG-3 in H5ts125-transformed rat embryo cells displaying an aggressive and progressed cancer phenotype. Oncogene (2000) 19, 3411 ± 3421.

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Section: Discussionmentioning

confidence: 99%

Cooperation between AP1 and PEA3 sites within the progression elevated gene-3 (PEG-3) promoter regulate basal and differential expression of PEG-3 during progression of the oncogenic phenotype in transformed rat embryo cells

Shi

Fisher

2000

Oncogene

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“…One possibility is that MMP-9 was secreted at a high level prior to E1AF gene transfection in QR-32 cells. Since the promoter region of MMP-2 has no E1AF/PEA3-binding site (Crawford and Matrisian, 1996;Matrisian, 1994), we speculate that the increased expression of MMP-2 and E1AF in QRsP cell lines was regulated by independent pathway or they are downstream events of some other upstream factor. E1AF/PEA3 is overexpressed in various metastatic cancer cells (Baert et al, 1997;Shindoh et al, 1996;Taguchi et al, 1997;Trimble et al, 1993;Wasylyk et al, 1993), and its activity is reported to be regulated by two distinct mitogenactivated protein kinases independently (O'Hagan et al, 1996).…”

Section: Metastatic Capacity Of E1af Transfectantsmentioning

confidence: 99%

Increased E1AF expression in mouse fibrosarcoma promotes metastasis through induction of MT1-MMP expression

et al. 1999

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In this study, we investigated the role of E1AF, a member of ets family transcription factor, in the acquisition of metastatic capacity by non-metastatic mouse ®brosarcoma cell clone, QR-32. The QR-32 cell clone grows progressively after co-implantation with gelatin sponge in syngeneic C57BL/6 mice. The cell lines (QRsP) established from arising tumors after the co-implantation exhibited enhanced tumorigenicity and pulmonary metastasis in vivo as compared with parent QR-32 cells. The enhanced pulmonary metastasis of QRsP cells was correlated well with augmented production of matrix metalloproteinase-2 (MMP-2) and increased expression of membrane-type 1-MMP (MT1-MMP). The QRsP cells also acquired higher chemokinetic activities to ®bronectin and higher invasive activities through a reconstituted basement membrane. Furthermore we observed the elevated mRNA expression of E1AF in QRsP cells compared to parent QR-32 cells. Therefore, we transfected QR-32 cells with E1AF cDNA. Overexpression of E1AF in the QR-32 cells resulted in the induction of MT1-MMP expression and converting an exogenously added precursor MMP-2 into active form. E1AF transfectants exhibited more motile and invasive activities, and moderately increased pulmonary metastatic activities than parental QR-32 cells in vivo, although their metastatic activities were lower than those of QRsP cells. These ®ndings suggest that the increased expression of E1AF in ®brosarcoma contributes to invasive phenotypes including MT1-MMP expression and enhanced cell migration, but not sucient for exhibiting highly metastatic activity in vivo.

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“…The unregulated expression of these enzymes has been associated with the propensity of tumor cells to metastasize (Kohn and Liotta, 1995). For example, PEA3 binding sites occur in the promoters of the serine proteinase urokinase-type plasminogen activator (Rorth et al, 1990;Nerlov et al, 1992) as well as the matrix metalloproteinases (MMP) gelatinase B (92 kDa type IV collagenase or MMP-9), interstitial collagenase (MMP-1), stromelysin-1 (transin or MMP-3), stromelysin-2 (MMP-10), stromelysin-3 (MMP-11) and matrilysin (pump-1 or MMP-7) (Matrisian, 1994;Higashino et al, 1995). PEA3 directly activates transcription from the MMP-1, MMP-9 and MMP-11 promoters (Higashino et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

HER2/Neu and the Ets transcription activator PEA3 are coordinately upregulated in human breast cancer

et al. 1997

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HER2/Neu is overexpressed in 25 ± 30% of all human breast cancers as a result of both gene ampli®cation and enhanced transcription. Transcriptional upregulation of HER2/neu leads to a 6 ± 8-fold increased abundance of its mRNA per gene copy and likely results from the elevated activity of transcription factors acting on the HER2/neu promoter. Here we report that transcripts of PEA3, an ETS transcription factor implicated in oncogenesis, were increased in 93% of HER2/Neuoverexpressing human breast tumor samples. Analyses to uncover the molecular basis for elevated PEA3 transcripts in HER2/Neu-positive breast tumors revealed that the HER2/Neu receptor tyrosine kinase initiated an intracellular signaling cascade resulting in increased PEA3 transcriptional activity; transcriptionally-activated PEA3 stimulated HER2/neu and PEA3 gene transcription by binding to sites in the promoters of these genes. PEA3 also activates transcription of genes encoding matrix-degrading proteinases, enzymes required for tumor cell migration and invasion. These ®ndings implicate PEA3 in the initiation and progression of HER2/Neu positive breast cancer, and suggest that PEA3 and signaling proteins a ecting its regulation are appropriate therapeutic targets.

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Matrix Metalloproteinase Gene Expression^a

Cited by 144 publications

References 42 publications

Cooperation between AP1 and PEA3 sites within the progression elevated gene-3 (PEG-3) promoter regulate basal and differential expression of PEG-3 during progression of the oncogenic phenotype in transformed rat embryo cells

Cooperation between AP1 and PEA3 sites within the progression elevated gene-3 (PEG-3) promoter regulate basal and differential expression of PEG-3 during progression of the oncogenic phenotype in transformed rat embryo cells

Increased E1AF expression in mouse fibrosarcoma promotes metastasis through induction of MT1-MMP expression

HER2/Neu and the Ets transcription activator PEA3 are coordinately upregulated in human breast cancer

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Matrix Metalloproteinase Gene Expressiona

Cited by 144 publications

References 42 publications

Cooperation between AP1 and PEA3 sites within the progression elevated gene-3 (PEG-3) promoter regulate basal and differential expression of PEG-3 during progression of the oncogenic phenotype in transformed rat embryo cells

Cooperation between AP1 and PEA3 sites within the progression elevated gene-3 (PEG-3) promoter regulate basal and differential expression of PEG-3 during progression of the oncogenic phenotype in transformed rat embryo cells

Increased E1AF expression in mouse fibrosarcoma promotes metastasis through induction of MT1-MMP expression

HER2/Neu and the Ets transcription activator PEA3 are coordinately upregulated in human breast cancer

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Matrix Metalloproteinase Gene Expression^a