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 elements

Abstract 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 csrc) dependent and was regulated transcriptionally through GT-box (252), and nuclear factor kB (NFkB; 2600) 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. NFkB function was associated with specific p50- and p65-containing nuclear NFkB binding complex(es). No function could be attributed to the proximal AP-1 (279) element, and minimal function was attributed to the SP-1 (2560), ets (2540), or distal AP-1 (2533) 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 NFkB element, in the transcriptional up-regulation of MMP-9 expression