Bouchard, Frédéric; Bélanger, Simon D.; Biron-Pain, Katherine et St-Pierre, Yves 
ORCID: https://orcid.org/0000-0002-1948-2041
(2010).
EGR-1 activation by EGF inhibits MMP-9 expression and lymphoma growth
Blood
, vol. 116
, nº 5.
pp. 759-766.
DOI: 10.1182/blood-2009-12-257030.
Résumé
Progression of hematological malignancies is strongly dependent on bi-directional interactions between tumor cells and stromal cells. Expression of members of the matrix metalloproteinase (MMP) family by stromal cells is a central event during these interactions. However, although several studies have focused on the mechanisms responsible for induction of MMP in stromal cells, the signals that negatively regulate their secretion of in these cells remain largely unknown. Here, we provide evidence that MMP-9 production by stromal cells is suppressed through activation of EGR-1, thereby inhibiting the growth of thymic lymphoma. We found that EGR-1 expression is induced in stromal cells following contact with lymphoma cells via EGF. Moreover, development of thymic lymphoma was inhibited when induced by lymphoma cells overexpressing EGF compared to control lymphoma cells. Using transgenic mice containing MMP-9 promoter-driven luciferase transgene in its genome, we further demonstrated that EGF/EGR-1 repressed transcriptional activation of the MMP-9 gene by stromal cells. De novo expression of EGR-1 alone by gene transfer or exposure to recombinant human EGF also inhibited MMP-9 expression. Taken together, these results indicate that EGR-1 could be a source of novel targets for therapeutic intervention in lymphoid tumors in which MMP-9 plays a critical role.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 29 juin 2024 20:51 |
| Dernière modification: | 29 juin 2024 20:51 |
| URI: | https://espace.inrs.ca/id/eprint/14432 |
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