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-G, 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 (-52), and nuclear factor κB (NFκB; -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. NFκB function was associated with specific p50- and p65-containing nuclear NFκB 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 NFκB 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.
|Number of pages||15|
|Journal||Cell Growth and Differentiation|
|Publication status||Published - May 1999|
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology