title: Growth hormone inhibits apoptosis in human colonic cancer cell lines: antagonistic effects of peroxisome proliferator activated receptor-gamma ligands.
abstract: GH has antiapoptotic effects on several cells. However, the antiapoptotic mechanisms of GH on colonic mucosa cells are not completely understood. Peroxisome proliferator activated receptor-gamma (PPARgamma) activation enhances apoptosis, and a link between GH and PPARgamma in the colonic epithelium of acromegalic patients has been suggested. We investigated the effects of GH and of PPARgamma ligands on apoptosis in colonic cancer cell lines. Colonic cells showed specific binding sites for GH, and after exposure to 0.05-50 nm GH, their apoptosis reduced by 45%. The antiapoptotic effect was due to either GH directly or GH-dependent local production of IGF-1. A 55-85% reduction of PPARgamma expression was observed in GH-treated cells, compared with controls (P < 0.05). However, treatment of the cells with 1-50 microm ciglitazone (cig), induced apoptosis and reverted the antiapoptotic effects of GH by increasing the programmed cell death up to 3.5-fold at 30 min and up to 1.7-fold at 24 h. Expression of Bcl-2 and TNF-related apoptosis-induced ligand was not affected by either GH or cig treatment, whereas GH reduced the expression of Bax, which was increased by cig treatment. In addition, GH increased the expression of signal transducer and activator of transcription 5b, which might be involved in the down-regulation of PPARgamma expression. In conclusion, GH may exert a direct antiapoptotic effect on colonic cells, through an increased expression of signal transducer and activator of transcription 5b and a reduction of Bax and PPARgamma. The reduced GH-dependent apoptosis can be overcome by PPARgamma ligands, which might be useful chemopreventive agents in acromegalic patients, who have an increased colonic polyps prevalence.
authors.affiliation: Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy. f.bogazzi@endoc.med.unipi.it
authors.forename: Fausto
authors.initials: F
authors.lastname: Bogazzi
authors.forename: Federica
authors.initials: F
authors.lastname: Ultimieri
authors.forename: Francesco
authors.initials: F
authors.lastname: Raggi
authors.forename: Dania
authors.initials: D
authors.lastname: Russo
authors.forename: Renato
authors.initials: R
authors.lastname: Vanacore
authors.forename: Chiara
authors.initials: C
authors.lastname: Guida
authors.forename: Sandra
authors.initials: S
authors.lastname: Brogioni
authors.forename: Chiara
authors.initials: C
authors.lastname: Cosci
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gasperi
authors.forename: Luigi
authors.initials: L
authors.lastname: Bartalena
authors.forename: Enio
authors.initials: E
authors.lastname: Martino
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D018938:Caco-2 Cells; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D019073:HT29 Cells; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008024:Ligands; D051379:Mice; D041681:NIH 3T3 Cells; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism*; D011986:Receptors, Somatotropin / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D007004:Hypoglycemic Agents; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D011986:Receptors, Somatotropin; D045162:Thiazolidinediones; D014157:Transcription Factors; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C039671:ciglitazone