Acromegalic patients have increased prevalence of colonic polyps. Development of hyperplastic polyps was related to suppressor of cytokine signalling (SOCS) 2 haploinsufficiency in animal models of acromegaly. OBJECTIVE AND PATIENTS: To evaluate whether variations in SOCS2 expression in the colonic mucosa of acromegalic patients might be associated to hyperplastic polyps, patients with active acromegaly or disease in remission with or without hyperplastic polyps were studied; controls were non-acromegalic subjects age- and sex- matched with or without polyps. MEASUREMENTS: Expression of SOCS1-3 was evaluated by RT-PCR, immunofluorescence and Western blot in the colonic mucosa. Coimmunoprecipatiton was used to evaluate multimeric protein complexes. RESULTS: Acromegalic patients with active disease and hyperplastic polyps had higher levels of SOCS2 transcripts; on the contrary, SOCS1 and SOCS3 transcripts did not differ among the study groups. While the expression of SOCS2 and SOCS3 protein was indistinguishable with that of the corresponding transcripts, SOCS1 protein expression was reduced in active acromegalic patients with polyps. SOCS1 protein was reduced owing to its increased proteasome degradation mediated by SOCS2. The increased SOCS2 and reduced SOCS1 led to increased STAT5b expression, suggesting a higher GH signalling transduction. CONCLUSIONS: Acromegalic patients with active disease and hyperplastic polyps have high levels of SOCS2 and increased SOCS1 degradation, leading to reduced negative feedback on GH signalling, likely favouring a hyperplastic polyps phenotype.
Changes in the expression of suppressor of cytokine signalling (SOCS) 2 in the colonic mucosa of acromegalic patients are associated with hyperplastic polyps
BOGAZZI, FAUSTO;MARTINO, ENIO
2009-01-01
Abstract
Acromegalic patients have increased prevalence of colonic polyps. Development of hyperplastic polyps was related to suppressor of cytokine signalling (SOCS) 2 haploinsufficiency in animal models of acromegaly. OBJECTIVE AND PATIENTS: To evaluate whether variations in SOCS2 expression in the colonic mucosa of acromegalic patients might be associated to hyperplastic polyps, patients with active acromegaly or disease in remission with or without hyperplastic polyps were studied; controls were non-acromegalic subjects age- and sex- matched with or without polyps. MEASUREMENTS: Expression of SOCS1-3 was evaluated by RT-PCR, immunofluorescence and Western blot in the colonic mucosa. Coimmunoprecipatiton was used to evaluate multimeric protein complexes. RESULTS: Acromegalic patients with active disease and hyperplastic polyps had higher levels of SOCS2 transcripts; on the contrary, SOCS1 and SOCS3 transcripts did not differ among the study groups. While the expression of SOCS2 and SOCS3 protein was indistinguishable with that of the corresponding transcripts, SOCS1 protein expression was reduced in active acromegalic patients with polyps. SOCS1 protein was reduced owing to its increased proteasome degradation mediated by SOCS2. The increased SOCS2 and reduced SOCS1 led to increased STAT5b expression, suggesting a higher GH signalling transduction. CONCLUSIONS: Acromegalic patients with active disease and hyperplastic polyps have high levels of SOCS2 and increased SOCS1 degradation, leading to reduced negative feedback on GH signalling, likely favouring a hyperplastic polyps phenotype.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
