Internalization-dependent regulation of HT29 cell proliferation by neurotensin.
In this study, we have investigated the involvement of the internalization process induced by neurotensin (NT) on MAP kinases Erk1/2 activation, inositol phosphates (IP) accumulation and cell growth in the human colonic cancer cell line HT29. Reversible blocking of NT/neurotensin receptor (NTR) complex endocytosis by hyperosmolar sucrose totally abolished both the phosphorylation of the MAP kinases Erk1/2 and the [3H]-thymidine incorporation induced by the peptide. By contrast, NT-evoked IP formation was not affected by sucrose treatment. These results therefore indicate that NT/NTR complex endocytosis triggers MAP kinase activation and subsequently the growth of HT29 cells. This property could be useful for the development of novel anticancer treatments.
Navarro
Valérie
V
Institut de Pharmacologie Moléculaire et Cellulaire, Unité Mixte de Recherche 6097 du Centre National de la Recherche Scientifique, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
Martin
Stéphane
S
Mazella
Jean
J
D001693:Biological Transport, Active; D049109:Cell Proliferation / Q000187:drug effects*; D004705:Endocytosis; D019073:HT29 Cells; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009496:Neurotensin / Q000378:metabolism* / Q000494:pharmacology*; D009994:Osmolar Concentration; D018028:Receptors, Neurotensin / Q000378:metabolism; D013395:Sucrose / Q000494:pharmacology
D007295:Inositol Phosphates; D018028:Receptors, Neurotensin; D009496:Neurotensin; D013395:Sucrose