All-trans-retinoic acid induces nuclear factor κB activation and matrix metalloproteinase-9 expression and enhances basement membrane invasivity of differentiation-resistant human SK-N-BE 9N neuroblastoma cells

Antonietta R. Farina, Maria Paola Masciulli, Antonella Tacconelli, Lucia Cappabianca, Giuseppina De Santis, Alberto Gulino, Andrew R. Mackay

Research output: Contribution to journalArticle

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Abstract

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 κB (NF-κB) 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-κB element (-600) in association with enhanced p50 mRNA expression, reduced cytoplasmic inhibitor of nuclear factor κBα protein levels, and the induction of nuclear p50/p65 containing MMP-9 NF-κB site binding activity. RA activation of the MMP-9 promoter was inhibited by transient overexpression of a dominant-negative inhibitor of nuclear factor κBα 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-κB transcription factor activity, which in turn induces MMP-9 expression and stimulation of basement membrane invasive capacity involving MMP-9 activity.

Original languageEnglish
Pages (from-to)343-354
Number of pages12
JournalCell Growth and Differentiation
Volume13
Issue number8
Publication statusPublished - 2002

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Matrix Metalloproteinase 9
Tretinoin
Neuroblastoma
Basement Membrane
Transcription Factors
Activator Appliances
Transcription Factor AP-1
Reporter Genes
Point Mutation
Proteins
Binding Sites
Cell Line
Messenger RNA

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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All-trans-retinoic acid induces nuclear factor κB activation and matrix metalloproteinase-9 expression and enhances basement membrane invasivity of differentiation-resistant human SK-N-BE 9N neuroblastoma cells. / Farina, Antonietta R.; Masciulli, Maria Paola; Tacconelli, Antonella; Cappabianca, Lucia; De Santis, Giuseppina; Gulino, Alberto; Mackay, Andrew R.

In: Cell Growth and Differentiation, Vol. 13, No. 8, 2002, p. 343-354.

Research output: Contribution to journalArticle

Farina, Antonietta R. ; Masciulli, Maria Paola ; Tacconelli, Antonella ; Cappabianca, Lucia ; De Santis, Giuseppina ; Gulino, Alberto ; Mackay, Andrew R. / All-trans-retinoic acid induces nuclear factor κB activation and matrix metalloproteinase-9 expression and enhances basement membrane invasivity of differentiation-resistant human SK-N-BE 9N neuroblastoma cells. In: Cell Growth and Differentiation. 2002 ; Vol. 13, No. 8. pp. 343-354.
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abstract = "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 κB (NF-κB) 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-κB element (-600) in association with enhanced p50 mRNA expression, reduced cytoplasmic inhibitor of nuclear factor κBα protein levels, and the induction of nuclear p50/p65 containing MMP-9 NF-κB site binding activity. RA activation of the MMP-9 promoter was inhibited by transient overexpression of a dominant-negative inhibitor of nuclear factor κBα 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-κB transcription factor activity, which in turn induces MMP-9 expression and stimulation of basement membrane invasive capacity involving MMP-9 activity.",
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AU - Masciulli, Maria Paola

AU - Tacconelli, Antonella

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AU - De Santis, Giuseppina

AU - Gulino, Alberto

AU - Mackay, Andrew R.

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