Jin Gang, Cao Zhigang, Sun Xilin, Wang Kai, Huang Tao, Shen Baozhong
Department of Medical Imaging, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China ; The No. 211 Hospital of the People's Liberation Army, Harbin, Heilongjiang 150086, P.R. China.
The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Oncol Lett. 2014 Aug;8(2):594-600. doi: 10.3892/ol.2014.2197. Epub 2014 May 28.
Protein O-glucosyltransferase 1 (POGLUT1) is a novel gene that was initially isolated and identified from the bone marrow cells of patients with myelodysplastic syndrome/acute myeloid leukemia. Previous findings have suggested that POGLUT1 promotes the proliferation of U937 human tissue lymphoma cells. Furthermore, POGLUT1 has been identified in other tissues, including the mammary glands, lymph nodes, intestine, liver and spleen. In the present study, in order to investigate the function and target of POGLUT1 in BT474 breast cancer cells, the effect of POGLUT1 on cell proliferation, differentiation, apoptosis and key proteins in the transforming growth factor (TGF)-β1 signaling pathway was investigated in BT474 cells. The overexpression of POGLUT1 in the presence of TGF-β1 was found to significantly enhance cell viability. Flow cytometric and quantitative polymerase chain reaction analyses revealed that POGLUT1 had an effect on the cell cycle and inhibited the TGF-β1-induced transcriptional upregulation of p16, a major cyclin-dependent kinase inhibitor (CDKI). Furthermore, phosphorylated (p)-Smad3, which has a key role in mediating the TGF-β antiproliferative response, was greatly inhibited by exogenous POGLUT1, suggesting a role for POGLUT1 in the TGF-β1-mediated signaling pathway in the BT474 cell cycle. However, no significant changes were observed in the expression of other CDKIs or in cell apoptosis. The findings of the present study show that the increase in BT474 cell viabilty induced by POGLUT1 is associated with POGLUT1-induced inhibition of the transcriptional upregulation of p16 by TGF-β1, which may be a result of the inhibition of p-Smad3.
蛋白O-葡萄糖基转移酶1（POGLUT1）是一种新基因，最初是从骨髓增生异常综合征/急性髓系白血病患者的骨髓细胞中分离并鉴定出来的。先前的研究结果表明，POGLUT1可促进U937人组织淋巴瘤细胞的增殖。此外，在包括乳腺、淋巴结、肠道、肝脏和脾脏在内的其他组织中也发现了POGLUT1。在本研究中，为了探究POGLUT1在BT474乳腺癌细胞中的功能和靶点，研究了POGLUT1对BT474细胞增殖、分化、凋亡以及转化生长因子（TGF）-β1信号通路中关键蛋白的影响。发现在TGF-β1存在的情况下，POGLUT1的过表达可显著提高细胞活力。流式细胞术和定量聚合酶链反应分析表明，POGLUT1对细胞周期有影响，并抑制了TGF-β1诱导的主要细胞周期蛋白依赖性激酶抑制剂（CDKI）p16的转录上调。此外，在外源性POGLUT1的作用下，在介导TGF-β抗增殖反应中起关键作用的磷酸化（p）-Smad3受到极大抑制，这表明POGLUT1在BT474细胞周期的TGF-β1介导的信号通路中发挥作用。然而，其他CDKIs的表达或细胞凋亡未观察到显著变化。本研究结果表明，POGLUT1诱导的BT474细胞活力增加与POGLUT1诱导的TGF-β1对p16转录上调的抑制有关，这可能是p-Smad3受到抑制的结果。
