XXXX cells with inactive nm23 show increased motility and response to motility factors.

@entity851 @entity5 @entity18962 @entity7790 @entity2533 @entity3 @entity694
@entity18962 has properties of a @entity3 suppressor gene. Although its mechanism of action is unknown, nm23 has been implicated in @entity2533 ( @entity2533 ) signal transduction. In an earlier study we decreased nm23 mRNA levels 2- to 8-fold by antisense phosphorothiolated oligonucleotides in two HT29 @entity694 sublines at different stages in @entity5 progression with different responses to @entity2533 : the HD3 subline, which shows @entity2533 -induced @entity851 and differentiation; and the more tumorigenic U9 subline, whose growth and invasion are stimulated by @entity2533 . Only @entity2533 -mediated responses in HD3 cells were inhibited by nm23 antisense oligos, suggesting that nm23 functions in only one @entity2533 signaling pathway. In the current report we have extended this study to cell motility. HD3 motility was increased by nm23 phosphorothiolated antisense oligos which decrease nm23 mRNA levels, while HD3 cell motility was conversely decreased by @entity2533 which increases nm23 mRNA levels. HD3 motility was not increased by basic FGF, @entity2533 or @entity7790 , while the 13-fold higher basal motility of U9 cells was stimulated 3-fold by basic FGF, 4-fold by @entity2533 and 5-fold by @entity7790 , but not by scatter factor. Differences in motility and response to motility factors could not be ascribed to differences in either basal levels of proteases or modulation of their levels by @entity2533 . Both HD3 and U9 cells displayed equal levels of urokinase activity and mRNA, equal expression of the metalloproteinase inhibitor TIMP-1, and no detectable collagenases by zymography. No differential response to @entity2533 was seen in any of these assays. Thus limited cell motility and lack of response to motility factors in HD3 @entity694 cells could be correlated with expression of nm23 active in signal transduction.
