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Cell Growth & Differentiation Vol. 10, 353-367, May 1999
© 1999 American Association for Cancer Research

Transcriptional Up-Regulation of Matrix Metalloproteinase-9 Expression during Spontaneous Epithelial to Neuroblast Phenotype Conversion by SK-N-SH Neuroblastoma Cells, Involved in Enhanced Invasivity, Depends upon GT-Box and Nuclear Factor {kappa}B Elements1

Antonietta R. Farina2, Antonella Tacconelli2, Alessandra Vacca, Marella Maroder, Alberto Gulino and Andrew R. Mackay3

Laboratory of Molecular Pathology, Department of Experimental Medicine, University of L’Aquila, Coppito II, 67100 L’Aquila [A. R. F., A. T., A. R. M.]; Neuromed Institute, 80077 Pozzilli [A. R. F., A. G., A. R. M.]; Department of Experimental Medicine and Pathology, University of Rome "La Sapienza," 00161 Rome [A. V., A. G.]; and Institute of Pathology, University of Palermo, 90141 Palermo [M. M.], Italy

Spontaneous epithelial (S) to neuroblast (N) conversion enhanced the capacity of SK-N-SH neuroblastoma (NB) cells to invade reconstituted basement membrane in vitro. This involved a switch to matrix metalloproteinase (MMP) activity, in particular MMP-9, and was associated with the induction of MMP-9 expression. N-type-specific MMP-9 expression was herbimycin A inhibitable tyrosine kinase (possibly c-src) dependent and was regulated transcriptionally through GT-box (-52), and nuclear factor {kappa}B (NF{kappa}B; -600) elements within the MMP-9 gene. GT-box function was associated with elevated levels of specific nuclear GT-box binding complexes in N-type cells. NF{kappa}B function was associated with specific p50- and p65-containing nuclear NF{kappa}B binding complex(es). No function could be attributed to the proximal AP-1 (-79) element, and minimal function was attributed to the SP-1 (-560), ets (-540), or distal AP-1 (-533) elements. This was despite elevated levels of specific junD/fra-1 containing proximal AP-1 element binding complex(es) in N-type cells. Our data highlight a pivotal role for the GT-box, in concert with the NF{kappa}B element, in the transcriptional up-regulation of MMP-9 expression during spontaneous S to N phenotype conversion by SK-N-SH cells involved in enhanced basement membrane invasivity.




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Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1999 by the American Association of Cancer Research.