BACKGROUND: The importance of the IGF system in HPT has been previously demonstrated. Additionally, the role of vitamin A in HPT has been reported. Retinoic acid (RA), a derivative of vitamin A, is a ligand for the IGF II receptor (IGF2R). We have evaluated the interactions of RA with the IGF system in a primary parathyroid cell culture model. MATERIALS AND METHODS: Primary cell cultures were prepared from nine patients. Following adhesion, the cells were transferred to serum-free medium and dosed once with growth factors +/- RA for 96 hours. Proliferation was assessed by measuring tritiated thymidine incorporation. RESULTS: Compared with the control group (100%), both IGF I and II increased DNA synthesis significantly. Retinoic acid significantly reduced the basal DNA synthesis to 82.2% +/- 4.2% compared with control (P < 0.05). Retinoic acid x10(-5) M completely abrogated the proliferative actions of IGF II (70.2% +/- 9.7%, P < 0.05) but had no significant effect on the IGF I response (P > 0.05). To evaluate the role of IGF2R or IGFBPs in mediating the actions of RA, the IGF II analogs [Leu27]IGF II (10-20-fold reduced IGF I receptor affinity) and des(1-6) IGF II (lower IGFBP binding affinity) were used. The IGF II inhibitory effect of RA was enhanced in the presence of analogs [Leu27]IGF II (P = 0.052) but not with des(1-6)IGF II (P > 0.05), compared with wild-type IGF II. CONCLUSIONS: These data implicate a novel antiproliferative role for RA in enhancing the pericellular clearance of IGF II via the IGF2R preventing ligand activation of the IGF I receptor. This may have broader implications for RA effects in other tumors.
BACKGROUND: The importance of the IGF system in HPT has been previously demonstrated. Additionally, the role of vitamin A in HPT has been reported. Retinoic acid (RA), a derivative of vitamin A, is a ligand for the IGF II receptor (IGF2R). We have evaluated the interactions of RA with the IGF system in a primary parathyroid cell culture model. MATERIALS AND METHODS: Primary cell cultures were prepared from nine patients. Following adhesion, the cells were transferred to serum-free medium and dosed once with growth factors +/- RA for 96 hours. Proliferation was assessed by measuring tritiated thymidine incorporation. RESULTS: Compared with the control group (100%), both IGF I and II increased DNA synthesis significantly. Retinoic acid significantly reduced the basal DNA synthesis to 82.2% +/- 4.2% compared with control (P < 0.05). Retinoic acid x10(-5) M completely abrogated the proliferative actions of IGF II (70.2% +/- 9.7%, P < 0.05) but had no significant effect on the IGF I response (P > 0.05). To evaluate the role of IGF2R or IGFBPs in mediating the actions of RA, the IGF II analogs [Leu27]IGF II (10-20-fold reduced IGF I receptor affinity) and des(1-6) IGF II (lower IGFBP binding affinity) were used. The IGF II inhibitory effect of RA was enhanced in the presence of analogs [Leu27]IGF II (P = 0.052) but not with des(1-6)IGF II (P > 0.05), compared with wild-type IGF II. CONCLUSIONS: These data implicate a novel antiproliferative role for RA in enhancing the pericellular clearance of IGF II via the IGF2R preventing ligand activation of the IGF I receptor. This may have broader implications for RA effects in other tumors.
Authors: N Martinet; F Alla; G Farré; T Labib; H Drouot; R Vidili; E Picard; M P Gaube; D Le Faou; J Siat; J Borelly; P Vermylen; T Bazarbachi; J M Vignaud; Y Martinet Journal: Cancer Res Date: 2000-06-01 Impact factor: 12.701
Authors: W Liu; P Hellman; Q Li; W R Yu; C Juhlin; H Nordlinder; O Rollman; G Akerström; H Törmä; H Melhus Journal: Biochem Biophys Res Commun Date: 1996-12-24 Impact factor: 3.575
Authors: S B Brown; T T Brierley; N Palanisamy; I B Salusky; W Goodman; M L Brandi; T B Drüeke; E Sarfati; P Ureña; R S Chaganti; J W Pike; A Arnold Journal: J Clin Endocrinol Metab Date: 2000-02 Impact factor: 5.958
Authors: Y Li; B Lin; A Agadir; R Liu; M I Dawson; J C Reed; J A Fontana; F Bost; P D Hobbs; Y Zheng; G Q Chen; B Shroot; D Mercola; X K Zhang Journal: Mol Cell Biol Date: 1998-08 Impact factor: 4.272
Authors: Giuseppe Cavallaro; Alessandra Cucina; Pierpaolo Coluccia; Luigi Petramala; Dario Cotesta; Andrea Polistena; Laura Zinnamosca; Claudio Letizia; Lodovico Rosato; Antonino Cavallaro; Giorgio De Toma Journal: World J Surg Date: 2010-01 Impact factor: 3.352