title: Pro-neurotensin/neuromedin N expression and processing in human colon cancer cell lines.
abstract: The regulatory peptide neurotensin NT has been proposed to exert an autocrine trophic effect on human colon cancers. In the present study, pro-neurotensin/neuromedin N (proNT/NN) expression and processing were investigated in 13 human colon cancer cell lines using a combination of radioimmunoassay and HPLC techniques. All 13 cell lines displayed low to moderate levels of proNT/NN ranging from 10 to 250 fmol/mg protein. However, only 6 (HCT8, LoVo, HT29, C119A, LS174T, and coloDM320) processed the precursor. Three of the latter (HCT8, LS174T, and coloDM320) were analysed in detail with regard to proNT/NN processing pattern and were found to produce NT and large precursor fragments ending with the NT or NN sequence. They had no detectable level of NN. Such a processing pattern resembles that generated by the prohormone convertase PC5. Northern and Western blot analysis of prohormone convertase expression in the 3 cell lines revealed that they were devoid of PC1 and PC2, whereas they all expressed PC5. These data indicate that proNT/NN is a good marker of human colon cancer cell lines while NT is found in only about half of the cell lines. They also suggest that, in addition to NT, several proNT/NN-derived products, possibly generated by PC5, might exert an autocrine positive effect on human colon cancer growth.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire du CNRS, Université de Nice-Sophia Antipolis, Valbonne, France.
authors.forename: C
authors.initials: C
authors.lastname: Rovère
authors.forename: P
authors.initials: P
authors.lastname: Barbero
authors.forename: J J
authors.initials: JJ
authors.lastname: Maoret
authors.forename: M
authors.initials: M
authors.lastname: Laburthe
authors.forename: P
authors.initials: P
authors.lastname: Kitabgi
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D009496:Neurotensin / Q000235:genetics* / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism*; D045706:Proprotein Convertase 2; D045702:Proprotein Convertase 5; D043484:Proprotein Convertases; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D013381:Subtilisins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D010446:Peptide Fragments; D011498:Protein Precursors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C042090:neuromedin N; D009496:Neurotensin; D045702:Proprotein Convertase 5; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D013381:Subtilisins; D045706:Proprotein Convertase 2; D016282:Aspartic Acid Endopeptidases