CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Farina, A. R.
Right arrow Articles by Mackay, A. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Farina, A. R.
Right arrow Articles by Mackay, A. R.
Cell Growth & Differentiation Vol. 13, 343-354, August 2002
© 2002 American Association for Cancer Research

All-trans-Retinoic Acid Induces Nuclear Factor {kappa}B Activation and Matrix Metalloproteinase-9 Expression and Enhances Basement Membrane Invasivity of Differentiation-resistant Human SK-N-BE 9N Neuroblastoma Cells1

Antonietta R. Farina, Maria-Paola Masciulli, Antonella Tacconelli, Lucia Cappabianca, Giuseppina De Santis, Alberto Gulino and Andrew R. Mackay2

Section of Molecular Pathology, Department of Experimental Medicine, University of L’Aquila, 67100 L’Aquila [A. R. F., M-P. M., A. T., L. C., G. DeS., A. R. M.], and Department of Experimental Medicine and Pathology, University of Rome "La Sapienza," 00161 Rome [A. G.], Italy

A comparison between retinoic acid (RA) differentiation-resistant and differentiation-sensitive SK-N-BE neuroblastoma (NB) cell lines revealed an association between resistance to differentiation, exhibited by N-myc stable transfected SK-N-BE 9N cells, with sensitivity to RA induction of p50/p65 nuclear factor {kappa}B (NF-{kappa}B) transcription factor activity and induction of matrix metalloproteinase (MMP)-9 expression leading to enhanced invasive behavior in vitro. These effects were not observed in differentiation-sensitive parental SK-N-BE or control-transfected SK-N-BE 2N counterparts. RA activated a MMP-9 promoter reporter gene construct in SK-N-BE 9N but not parental SK-N-BE or SK-N-BE 2N cells through a NF-{kappa}B element (–600) in association with enhanced p50 mRNA expression, reduced cytoplasmic inhibitor of nuclear factor {kappa}B{alpha} protein levels, and the induction of nuclear p50/p65 containing MMP-9 NF-{kappa}B site binding activity. RA activation of the MMP-9 promoter was inhibited by transient overexpression of a dominant-negative inhibitor of nuclear factor {kappa}B{alpha} protein and stimulated by transient p50 but not p65 overexpression in the absence of RA. A limited, nonessential function for activator protein 1 (–74), Ets (–540), and SP1 (–560) elements within the MMP-9 promoter was revealed by point mutation but was not associated with changes in the binding or position of complexes constitutive to differentiation-sensitive or -resistant cells. Our data indicates that in this model of NB resistance to differentiation that results from uncoupled RA regulation of N-myc expression, RA stimulates malignant NB cell behavior by inducing nuclear NF-{kappa}B transcription factor activity, which in turn induces MMP-9 expression and stimulation of basement membrane invasive capacity involving MMP-9 activity.




This article has been cited by other articles:


Home page
J. Immunol.Home page
S. Darmanin, J. Chen, S. Zhao, H. Cui, R. Shirkoohi, N. Kubo, Y. Kuge, N. Tamaki, K. Nakagawa, J.-i. Hamada, et al.
All-trans Retinoic Acid Enhances Murine Dendritic Cell Migration to Draining Lymph Nodes via the Balance of Matrix Metalloproteinases and Their Inhibitors
J. Immunol., October 1, 2007; 179(7): 4616 - 4625.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 2002 by the American Association of Cancer Research.