Globular adiponectin, acting via adiponectin receptor-1, inhibits leptin-stimulated oesophageal adenocarcinoma cell proliferation
Globular adiponectin, acting via adiponectin receptor-1, inhibits leptin-stimulated oesophageal adenocarcinoma cell proliferation
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DOI：
10.1016/j.mce.2008.01.023
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发表时间：
2008-03-26
影响因子：
4.1
通讯作者：
Beales, Ian L. P.
中科院分区：
文献类型：
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作者：
Ogunwobi, Olorunseun O.;Beales, Ian L. P.
肥胖会增加患多种癌症的风险，包括食管腺癌（OAC）。肥胖的特征是高瘦素血症和低脂联素血症：我们假设这些激素因素可能有助于OAC的进展。我们研究了瘦素和脂联素对OAC细胞增殖的影响。瘦素刺激四种不同OAC系（OE 33、OE 19、BIC-1和FLO）的增殖，并且这被球状脂联素抑制，但不被全长脂联素抑制。所有四个OAC系均表达两种脂联素受体亚型（AdipoR 1和AdipoR 2）。球状脂联素也抑制瘦素诱导的大鼠IEC-18细胞只表达AdipoR 1的增殖。5-AMP活化蛋白激酶（化合物Q）和丝氨酸/苏氨酸磷酸酶（冈田酸）的特异性抑制剂和针对AdipoR 1的特异性siRNA阻断了脂联素的抗增殖作用。脂联素抑制瘦素诱导的Akt磷酸化;该作用对冈田酸敏感，但对化合物C不敏感。脂联素缺乏可能促进OAC在肥胖中的表达。(c)2008爱思唯尔爱尔兰有限公司保留所有权利。
Obesity increases the risk of developing several cancers including oesophageal adenocarcinoma (OAC). Obesity is characterised by hyperleptinaema and hypoadiponectinaemia: we have hypothesised that these hormonal factors may contribute to the progression of OAC. We have examined the effects of leptin and adiponectin on proliferation of OAC cells. Leptin-stimulated proliferation in four different OAC lines (OE33, OE19, BIC-1 and FLO) and this was inhibited by globular but not full length adiponectin. All four OAC lines expressed both adiponectin-receptor isoforms (AdipoR1 and AdipoR2). Globular adiponectin also inhibited leptin-induced proliferation in rat IEC-18 cells which only expressed AdipoR1. Specific inhibitors of 5-AMP-activated protein kinase (Compound Q and serine/threonine phosphatases (okadaic acid) and a specific siRNA to AdipoR1 blocked the anti-proliferative effects of adiponectin. Adiponectin inhibited leptin-induced Akt phosphorylation; this action was sensitive to okadaic acid but not to Compound C. Adiponectin deficiency may contribute to the promotion of OAC in obesity. (c) 2008 Elsevier Ireland Ltd. All rights reserved.