Obestatin in human neuroendocrine tissues and tumours: expression and effect on tumour growth
Obestatin in human neuroendocrine tissues and tumours: expression and effect on tumour growth
复制标题
肥胖抑制素在人类神经内分泌组织和肿瘤中的表达及其对肿瘤生长的影响
DOI：
10.1002/path.2551
复制
发表时间：
2009
期刊：
影响因子：
--
通讯作者：
M. Papotti
中科院分区：
文献类型：
--
作者：
M. Volante;R. Rosas;P. Ceppi;I. Rapa;P. Cassoni;B. Wiedenmann;F. Settanni;R. Granata;M. Papotti
来自与生长激素释放肽相同的前体并且其受体仍然未被识别的激素obestatin具有多种代谢/调节功能，主要与食物摄取抑制和胃肠运动减少相关。肥胖抑制素在人体正常组织和肿瘤组织中的分布尚不清楚。我们报告在胎儿组织样本中，在甲状腺、垂体、肺、胰腺和胃肠道中检测到obestatin肽，通常与嗜铬粒蛋白A共定位。在成人组织中，obestatin蛋白表达仅限于垂体、肺、胰腺和胃肠道，并与ghrelin严格共定位。相比之下，在内分泌肿瘤中，obestatin在一小部分甲状腺、甲状旁腺、胃肠道和胰腺肿瘤中表达，在大多数情况下具有局灶性免疫反应性，并与ghrelin共定位。在正常和肿瘤样本中，生长素释放肽和肥胖抑制素特异性片段的信使RNA水平相当，证实了翻译后机制而不是选择性剪接事件导致生长素释放肽/肥胖抑制素产生。最后，在TT和BON-1细胞系中，在药理学剂量下，obestatin诱导抗增殖作用，与ghrelin观察到的相反。总之，我们的数据表明，obestatin是由相同的内分泌细胞，表达生长激素释放肽在正常组织从胎儿到成人的生活，而相比，生长激素释放肽，在肿瘤条件下，它是下调的翻译后调节，并显示出潜在的体外抗增殖特性。版权所有© 2008大不列颠及爱尔兰病理学会。由John Wiley & Sons有限公司出版
The hormone obestatin, which is derived from the same precursor as ghrelin and whose receptor(s) is still unrecognized, possesses a variety of metabolic/modulatory functions mostly related to food intake suppression and reduction of gastrointestinal motility. The distribution of obestatin in normal and neoplastic human tissues is poorly understoood. We report that in fetal tissue samples, obestatin peptide was detected in the thyroid, pituitary, lung, pancreas and gastrointestinal tract, usually being co‐localized with chromogranin A. In adult tissues, obestatin protein expression was restricted to pituitary, lung, pancreas and gastrointestinal tract and was co‐localized strictly with ghrelin. By contrast, in endocrine tumours obestatin was expressed in a small fraction of thyroid, parathyroid, gastrointestinal and pancreatic neoplasms, in most cases with a focal immunoreactivity and co‐localized with ghrelin. Messenger RNA levels of the specific fragments of ghrelin and obestatin were comparable in both normal and tumour samples, confirming that post‐translational mechanisms rather than alternative splicing events lead to ghrelin/obestatin production. Finally, in TT and BON‐1 cell lines obestatin induced antiproliferative effects at pharmacological doses, opposite to those observed with ghrelin. In summary, our data demonstrate that obestatin is produced by the same endocrine cells that express ghrelin in normal tissues from fetal to adult life, whereas, as compared to ghrelin, in neoplastic conditions it is down‐regulated by post‐translational modulation and shows potential antiproliferative properties in vitro. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
肥胖抑制素在大鼠体内的分布和生物活性。
DOI：
10.1677/joe.1.06944
发表时间：
2006
期刊：
The Journal of endocrinology
影响因子：
--
作者：
Dun,SiokL;Brailoiu,GCristina;Brailoiu,Eugen;Yang,Jun;Chang,JawKang;Dun,NaeJ
通讯作者：
Dun,NaeJ