Growth hormone receptor (GHR), the cognate receptor of growth hormone (GH), is a membrane bound receptor that belongs to the class I cytokine receptor superfamily. GH binding GHR induces cell differentiation and maturation, initiates the anabolism inside the cells and promotes cell proliferation. Recently, GHR has been reported to be associated with various types of cancer. However, the underlying mechanism of GHR in gastric cancer has not been defined. Our results showed that silence of GHR inhibited the growth of SGC‐7901 and MGC‐803 cells, and tumour development in mouse xenograft model. Flow cytometry showed that GHR knockout significantly stimulated gastric cancer cell apoptosis and caused G1 cell cycle arrest, which was also verified by Western blot that GHR deficiency induced the protein level of cleaved‐PARP, a valuable marker of apoptosis. In addition, GHR deficiency inhibited the activation of PI3K/AKT signalling pathway. On the basis of the results, that GHR regulates gastric cancer cell growth and apoptosis through controlling G1 cell cycle progression via mediating PI3K/AKT signalling pathway. These findings provide a novel understanding for the role of GHR in gastric cancer.

中文翻译：

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GHR 通过 PI3K/AKT 信号传导参与胃细胞生长和凋亡

生长激素受体(GHR)是生长激素(GH)的同源受体，是一种膜结合受体，属于I类细胞因子受体超家族。GH 结合 GHR 诱导细胞分化和成熟，启动细胞内的合成代谢并促进细胞增殖。最近，据报道，GHR 与多种类型的癌症有关。然而，GHR 在胃癌中的潜在机制尚未明确。我们的结果表明，GHR 的沉默抑制了 SGC-7901 和 MGC-803 细胞的生长，以及小鼠异种移植模型中的肿瘤发展。流式细胞术显示GHR敲除显着刺激胃癌细胞凋亡并导致G1细胞周期停滞，Western blot也证实GHR缺陷诱导了cleaved-PARP的蛋白水平，这是细胞凋亡的一个有价值的标志物。此外，GHR缺陷抑制PI3K/AKT信号通路的激活。结果表明，GHR通过介导PI3K/AKT信号通路控制G1细胞周期进程来调节胃癌细胞的生长和凋亡。这些发现为 GHR 在胃癌中的作用提供了新的认识。