Moreover, suppression of vasoactive intestinal peptide (VIP) expression alone induced neuroblastoma cell differentiation, and VIP was up-regulated by TG2-L, but not TG2-S. Taken together, our data indicate that TG2-L and TG2-S exert opposite effects on cell differentiation due to differences in GTP binding and modulation of VIP gene transcription.
The resemblance of the signaling pathways involving concomitant activities of PKC, ERK1/2 and PKA in PACAP regulation of the FOS and VIP gene expressions suggest for the first time a role of FOS in PACAP-induced VIP gene expression in human NB-1 neuroblastoma cells.
To determine whether VIP could modulate MYCN expression, we carried out real-time quantitative RT-PCR and Western immunoblot analyses in human neuroblastoma SH-SY5Y and IMR-32 cells.
Taken together, these data support the hypothesis that VIP modulation of neural crest differentiation is mediated via VPAC1 and that high expression of VPAC1 induces differentiation in and decreases tumorigenicity of neuroblastoma cells.
SK-N-SH human neuroblastoma subclones differ widely in basal and second messenger induction of the gene encoding the neuropeptide vasoactive intestinal peptide (VIP).
We therefore investigated whether PACAP affected the VIP gene expression and elucidated the molecular mechanisms using the human neuroblastoma cell line NB-1.
To investigate the molecular mechanisms by which activin regulates neuronal gene expression, we have examined activin's regulation of VIP gene expression in NBFL neuroblastoma cells.
Here we present data on the effects of retinoic acid (RA), a known modulator of neuronal differentiation, on VIP gene expression in the human neuroblastoma cell line NB-1.
Conversely, the VIP analog was found to displace VIP from its binding sites on LA-N-2 human neuroblastoma cells (VIP IC50: 5.4 nM; VIP analog IC50: 52.2 nM) and to inhibit the VIP-induced cyclic AMP production of 58 +/- 15% at 1 microM and 95 +/- 2% at 10 microM.
Concomitant enhancement of both intracellular and extracellular VIP expression, coupled with the induction of functional specific VIP receptors during VIP-induced differentiation, provides critical evidence for the autocrine regulation of neuroblastoma maturation by this peptide.
These and other data indicate that multiple transcriptional elements control VIP expression in neuroblastoma cells and are candidates as mediators of VIP gene expression in the intact animal.
Functional vasoactive intestinal polypeptide (VIP) receptors in human neuroblastoma subclones that contain VIP precursor mRNA and release VIP-like substances.