Vasoactive intestinal peptide stimulates proliferation in HT29 human colonic adenocarcinoma cells: concomitant activation of Ras/Rap1-B-Raf-ERK signalling pathway.
The vasoactive intestinal peptide (VIP) has been shown to regulate cell proliferation and differentiation in many cell types. We previously reported that this neuropeptide inhibited proliferation in HT29 adenocarcinoma cells cultured in serum-containing medium. In addition, it has been demonstrated that VIP induced a potent stimulation of intracellular cAMP production in these cells cultured either in the absence or in the presence of serum. We also demonstrated that VIP induced phosphorylation of the small GTPase Rap1 in these cancerogenous cells. In the present study, the effects of VIP on the proliferation of HT29 cells cultured in the absence of growth factors and various concomitant signalling events were investigated. Under serum-free conditions VIP stimulates HT29 cell proliferation and induced a time- and concentration-dependent ERK activation. Furthermore, VIP induced the activation of the small GTPase Rap1 and of a 95 kDa isoform of the serine/threonine kinase B-Raf. Ras GTPase is also activated in VIP-stimulated cells. We hypothesize that VIP-induced proliferation in HT29 adenocarcinoma cells may involve a cAMP-Rap1/Ras-B-Raf-ERK signalling pathway.
Equipe de Biologie des Interactions Cellulaires, CNRS UMR 6558 LBSC, Université de Poitiers, 40 avenue du Recteur Pineau, 86022, Poitiers Cedex, France.
Céline
C
Alleaume
Alain
A
Eychène
Evelyne
E
Caigneaux
Jean-Marc
JM
Muller
Michel
M
Philippe
D002455:Cell Division / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007202:Indicators and Reagents; D010957:Plasmids / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D020827:rap1 GTP-Binding Proteins / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics*
D007202:Indicators and Reagents; D014660:Vasoactive Intestinal Peptide; D019204:GTP-Binding Proteins; D020827:rap1 GTP-Binding Proteins; D018631:ras Proteins