All-trans retinoic acid (ATRA) downregulates MMP-9 by modulating its regulatory molecules.
The vitamin A derivative all-trans retinoic acid (ATRA) is considered as a potent chemotherapeutic drug for its capability of regulating cell growth and differentiation. We aimed to study the effect of ATRA on MMP-9 in MDA-MB-231, human breast cancer cells and the probable molecular mechanisms through which ATRA exerts its effect.


RESULTS
Our experimental findings demonstrate that ATRA enters into the nucleus and regulates various signaling pathways viz. Integrin, FAK, ERK, PI-3K, NF-κB and also EGFR and down regulates pro-MMP-9 activity as well as its expression. As a result MDA-MB-231 cell migration on fibronectin medium gets retarded in presence of ATRA. ATRA up regulates TIMP-1 expression. Our study may help to understand the role of ATRA as a regulator of MMP-9 and the possible signaling pathways which are involved in this ATRA mediated down regulation of MMP-9.
Dutta
Anindita
A
Department of Receptor Biology & Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata, India.
Sen
Triparna
T
Chatterjee
Amitava
A
D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D066246:ErbB Receptors / Q000378:metabolism; D005353:Fibronectins / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008024:Ligands; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015820:Cadherins; D003470:Culture Media; D005353:Fibronectins; D016023:Integrins; D008024:Ligands; D016328:NF-kappa B; D018168:Receptors, Retinoic Acid; D019715:Tissue Inhibitor of Metalloproteinase-1; D042461:Vascular Endothelial Growth Factor A; C082927:retinoic acid binding protein I, cellular; D014212:Tretinoin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020780:Matrix Metalloproteinase 9