This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Farina, A. R. Articles by Mackay, A. R. Search for Related Content PubMed PubMed Citation Articles by Farina, A. R. Articles by Mackay, A. R.

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

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 B (NF-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-B element (–600) in association with enhanced p50 mRNA expression, reduced cytoplasmic inhibitor of nuclear factor B protein levels, and the induction of nuclear p50/p65 containing MMP-9 NF-B site binding activity. RA activation of the MMP-9 promoter was inhibited by transient overexpression of a dominant-negative inhibitor of nuclear factor B 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-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:

				O. Chayka, D. Corvetta, M. Dews, A. E. Caccamo, I. Piotrowska, G. Santilli, S. Gibson, N. J. Sebire, N. Himoudi, M. D. Hogarty, et al. Clusterin, a Haploinsufficient Tumor Suppressor Gene in Neuroblastomas J Natl Cancer Inst, May 6, 2009; 101(9): 663 - 677. [Abstract] [Full Text] [PDF]

				A. Druilhe, J.-M. Zahm, L. Benayoun, D. El Mehdi, M. Grandsaigne, M.-C. Dombret, I. Mosnier, B. Feger, J. Depondt, M. Aubier, et al. Epithelium Expression and Function of Retinoid Receptors in Asthma Am. J. Respir. Cell Mol. Biol., March 1, 2008; 38(3): 276 - 282. [Abstract] [Full Text] [PDF]

				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]