Human adiponectin inhibits cell growth and induces apoptosis in human endometrial carcinoma cells, HEC-1-A and RL95-2

被引:103
作者
Cong, Li
Gasser, Jessica
Zhao, Jessica
Yang, Baofeng
Li, Fanghong
Zhao, Allan Z.
机构
[1] Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA
[2] Harbin Med Coll, Affiliated Hosp 1, Dept Endocrinol & Metab, Harbin 150085, Peoples R China
关键词
D O I
10.1677/ERC-07-0065
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Obesity is one of the well-established risk factors for endometrial cancer. Recent clinical studies have demonstrated that circulating adiponectin concentrations are inversely correlated with the incidence of endometrial carcinoma. Such epidemiological findings are consistent with the paradoxical observations that adiponectin levels are reduced in obesity. This study investigated the direct eff ects of adiponectin on two endometrial carcinoma cell lines, HEC-1-A and RL95-2. These cell lines express both variants of adiponectin receptors, adipo-R1 and adipo-R2. Adiponectin treatment leads to suppression of cell proliferation in both cell types, which is primarily due to the significant increase of cell populations at G(1)/G(0)-phase and to the induction of apoptosis. The inhibition of growth in these two cell lines appears to be mediated by different signaling pathways. Although adiponectin treatment markedly increases the phosphorylation (Thr1 72) of AMP-activated protein kinase a in both HEC-1 -A and RL95-2 within 30 min, prolonged exposure (48 h) leads to inactivation of Akt as well as reduction of cyclin D1 protein expression in HEC-11 -A cells. In contrast, similar treatment of RL95-2 cells with adiponectin, while having no effects on Akt activity and cyclin D1 expression, causes a decrease in cyclin E2 expression and the activity of mitogen-activated kinase (p42/44). We conclude that adiponectin exerts direct anti-proliferative effects on HEC-11-A and RL95-2 cells by inducing cell cycle arrest and apoptosis. Depending on the genotypes of the endometrial cancer cells, the inhibitory effects of adiponectin are associated with the reduction of different pro-growth regulators of cell cycle and signaling proteins. Our study thus provides a cellular mechanism underlying the linkages between endometrial cancer and obesity.
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收藏
页码:713 / 720
页数:8
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