Induction of matrix metalloprotease-1 gene expression by retinoic acid in the human pancreatic tumour cell line Dan-G

Marschall, Zofia von; Riecken, Ernst–Otto; Rosewicz, Stefan

doi:10.1038/sj.bjc.6690446

Cited by 6 publications

(4 citation statements)

References 27 publications

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“…All-trans RA is an inhibitor of MMP gene expression in other cell types (9,51); however, recent reports demonstrate atRA-induced MMP protein expression in NHKs (52). This suggests that MMP gene expression may be regulated differently by atRA in epithelia in comparison with fibroblastic cell types (52,53). Our data support this finding and indicate that atRA may impact MMP-1 expression through both transcriptional and post-transcriptional mechanisms (Fig.…”

Section: Discussionsupporting

confidence: 82%

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Interaction between the Aryl Hydrocarbon Receptor and Retinoic Acid Pathways Increases Matrix Metalloproteinase-1 Expression in Keratinocytes

Murphy

Villano

Dorn

et al. 2004

Journal of Biological Chemistry

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Exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in a variety of pathological lesions in humans via activation of the aryl hydrocarbon receptor (AhR) pathway. It has become apparent that this pathway interacts with a variety of signaling pathways that are believed to be involved in mediating TCDD/AhR biological effects. Our hypothesis is that TCDD mediates these pathological lesions by directly altering the expression of genes involved in matrix deposition and remodeling and that the retinoic acid signaling pathway is involved in modulating TCDD-induced effects. Therefore, we examined the effect of TCDD and all-trans retinoic acid (atRA) on the expression of matrix metalloproteinase-1 (MMP-1, interstitial collagenase), one of the proteolytic enzymes that degrade type I collagen, in normal human keratinocytes. The data show that TCDD exposure results in increased MMP-1 expression in keratinocytes that is further enhanced by co-treatment with all-trans retinoic acid. TCDD-induced expression of MMP-1 appears to be mediated through two AP-1 elements in the proximal promoter of the MMP-1 gene. However, retinoic acid-mediated induction of keratinocyte MMP-1 is a result of both promoter activation and increased mRNA stability. These findings are the first to demonstrate TCDD-induced expression of MMP-1 and to demonstrate interactions between the TCDD/AhR and retinoic acid pathways on MMP-1 expression.Exposure to the polycyclic aromatic hydrocarbon 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) 1 results in a number of pathological lesions involving matrix deposition and tissue remodeling, including prostate and mammary tubule morphogenesis, palatal development, and tumor promotion (1-3). We hypothesize that TCDD mediates these pathological lesions by altering the expression of genes involved in matrix remodeling.Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade the protein components of the extracellular matrix. MMP expression is integral to processes in skin remodeling and inappropriate expression and activity of MMPs is associated with a variety of pathologies such as rheumatoid arthritis and tumor metastasis (4 -6). Regulation of MMPs occurs primarily at the levels of transcription and activity (7). Investigation into MMP gene expression have identified several cis-and trans-acting factors that are involved in MMP-1 transcriptional activation, including several AP-1 sites and PEA-3 elements, that contribute to MMP-1 gene expression (8, 9).The primary mechanism of TCDD-induced changes in gene expression is through activation of the aryl hydrocarbon receptor (AhR)/aryl hydrocarbon receptor nuclear translocator (Arnt) transcription pathway. AhR and its dimerization partner, Arnt, are members of the basic helix-loop-helix PAS (bHLH-PAS) domain family of transcription factors. Proteins in this family have diverse biological roles ranging from regulation of development, hypoxia signaling, and circadian rhythms (reviewed in Ref.

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Section: Discussionsupporting

confidence: 82%

“…Therefore, the increase in steady state MMP-1 mRNA following TCDD-atRA co-treatment results from a slight increase in transcription in addition to an increase in MMP-1 mRNA stability. Increased MMP-1 mRNA stability following atRA treatment has also been observed by other laboratories (53).…”

Section: Discussionsupporting

confidence: 55%

Interaction between the Aryl Hydrocarbon Receptor and Retinoic Acid Pathways Increases Matrix Metalloproteinase-1 Expression in Keratinocytes

Murphy

Villano

Dorn

et al. 2004

Journal of Biological Chemistry

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“…Similarly, cortisol increases the half‐life of MMP‐13 mRNA twofold in rat osteoblasts (Delany et al, 1995), while the MMP‐9 mRNA is stabilized in response to α3β1 integrin in immortalized mouse keratinocytes (Lyer et al, 2005). In addition, several pharmacological reagents including doxycycline (Liu et al, 2003), all‐ trans retinoic acid (Murphy et al, 2004), 13‐ cis retinoic acid (von Marschall et al, 2006), and 1α,25‐dihydrovitamin D3 (Bao et al, 2006) regulate MMP expression by affecting mRNA stability.…”

Section: Post‐transcriptional Regulation Of Mmp Gene Expressionmentioning

confidence: 99%

Regulation of matrix metalloproteinase gene expression

Yan

Boyd

2006

Journal Cellular Physiology

640

568

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The metalloproteinases degrade extracellular matrix (ECM) components and activate growth factors, thereby contributing to physiological events (tissue remodeling in pregnancy, wound healing, angiogenesis) and pathological conditions (cancer, arthritis, periodontitis). The intent of this review is to bring together various studies on transcriptional and post-transcriptional control of metalloproteinase expression. Certainly, much information is known as to the cis-elements and corresponding trans-activators regulating expression of these genes. We discuss the fact that a number of the metalloproteinase promoters share common structural features and, therefore, not surprisingly are co-regulated in their expression to some extent. More recently, much effort has been devoted to understanding the role of chromatin in regulating gene expression. While this area has been understudied with respect to matrix metalloproteinase (MMP) regulation, the literature indicates a convincing role for both histone modifications and chromatin-remodeling motors in controlling expression of multiple metalloproteinases. In addition to transcriptional control, mRNA stability and protein translation also contribute to the metalloproteinase product amount. We discuss such studies and how various biological cues, including TGF-b, regulate the levels of certain collagenases either solely through mRNA stabilization or by jointly targeting transcriptional and post-transcriptional mechanisms. We also discuss the current deficits in our knowledge, concerning tissue-specific expression and why despite elevated amounts/activity of trans-activators targeting MMP promoters in tumor cells, nevertheless, MMP expression is largely restricted to the stromal compartment. Finally, we argue for potential technologies to regulate MMP expression of utility in pathological conditions where these enzymes are aberrantly expressed.J cis-Elements and trans-Activators Regulating MMP Gene ExpressionAmple evidence indicates that MMP gene expression is, to a large extent, regulated at the transcriptional level. Indeed, the MMP promoters harbor several cis-elements allowing for the regulation of MMP gene expression by a diverse set of trans-activators including AP-1, PEA3, Sp-1, b-catenin/Tcf-4, and NF-kB (Fig. 1). Several of the MMP promoters are strikingly similar ( Fig. 1) and, in fact, share several cis-elements (Fig. 1), consistent with observations that some MMPs are co-regulated in their expression. In contrast, and somewhat surprisingly, the composition of the promoters of functionally related MMPs such as MMP-2/MMP-9 (gelatinase) or MMP-1/MMP-8 (collagenase) are distinct. Based on the composition of cis-elements, the MMP promoters can be roughly grouped into three categories (Fig. 1). The first group, including the majority of the MMP promoters, contains a TATA box at approximately À30 bp (relative to the transcription start site) and an AP-1-binding site at approximately À70 bp. Most of these promoters also contain an upstream PEA3-binding site that is ofte...

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“…Not all of these mechanisms are transcriptional; for example, retinoids were suggested to affect RNA stability (18). We have analyzed mRNA stability of IGFBP3, TGFBI, UBD, and EPLIN during 24-hour treatment with actinomycin D and found these messages to be as stable as h-actin mRNA, with no detectable effect of RA on their stability (19).…”

Section: Discussionmentioning

confidence: 99%

Agonist and Antagonist of Retinoic Acid Receptors Cause Similar Changes in Gene Expression and Induce Senescence-like Growth Arrest in MCF-7 Breast Carcinoma Cells

et al. 2006

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Biological effects of retinoids are mediated via retinoic acid (RA) receptors (RAR) and retinoid X receptors (RXR). The best-characterized mechanism of retinoid action is stimulation of transcription from promoters containing RA response elements (RARE). Retinoids induce senescence-like growth arrest in MCF-7 breast carcinoma cells; this effect is associated with the induction of several growth-inhibitory genes. We have now found that these genes are induced by RAR-specific but not by RXR-specific ligands. Genome-scale microarray analysis of gene expression was used to compare the effects of two pan-RAR ligands, one of which is a strong agonist of RARE-dependent transcription, whereas the other induces such transcription only weakly and antagonizes the inducing effect of RAR agonists. Both RAR ligands, however, produced very similar effects on gene expression in MCF-7 cells, suggesting that RARE-dependent transcription is only a minor component of retinoid-induced changes in gene expression. The effects of RAR ligands on gene expression parallel changes associated with damage-induced senescence, and both ligands induced G 1 arrest and the senescent phenotype in MCF-7 cells. The RAR ligands up-regulated many tumor-suppressive genes and down-regulated multiple genes with oncogenic activities. Genes that are strongly induced by RAR ligands encode secreted bioactive proteins, including several tumor-suppressing factors. In agreement with these observations, retinoid-treated MCF-7 cells inhibited the growth of retinoid-insensitive MDA-MB-231 breast carcinoma cells in coculture. These results indicate that RARE-independent transcriptional effects of RAR ligands lead to senescence-like growth arrest and paracrine growthinhibitory activity in MCF-7 breast carcinoma cells. (Cancer Res 2006; 66(17): 8749-61)

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Induction of matrix metalloprotease-1 gene expression by retinoic acid in the human pancreatic tumour cell line Dan-G

Cited by 6 publications

References 27 publications

Interaction between the Aryl Hydrocarbon Receptor and Retinoic Acid Pathways Increases Matrix Metalloproteinase-1 Expression in Keratinocytes

Interaction between the Aryl Hydrocarbon Receptor and Retinoic Acid Pathways Increases Matrix Metalloproteinase-1 Expression in Keratinocytes

Regulation of matrix metalloproteinase gene expression

Agonist and Antagonist of Retinoic Acid Receptors Cause Similar Changes in Gene Expression and Induce Senescence-like Growth Arrest in MCF-7 Breast Carcinoma Cells

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