Epidermal growth factor receptor-related protein inhibits cell growth and induces apoptosis of BxPC3 pancreatic cancer cells.
Epidermal growth factor receptor-related protein inhibits cell growth and induces apoptosis of BxPC3 pancreatic cancer cells.
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DOI：
10.1158/0008-5472.can-04-3654
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发表时间：
2005-05
期刊：
影响因子：
11.2
通讯作者：
Yuxiang Zhang;Sanjeev Banerjee;Zhiwei Wang;Dorota J. Marciniak;A. Majumdar;F. Sarkar
中科院分区：
文献类型：
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作者：
Yuxiang Zhang;Sanjeev Banerjee;Zhiwei Wang;Dorota J. Marciniak;A. Majumdar;F. Sarkar
表皮生长因子受体（EGFR）信号网络的失调在胰腺癌中经常被报道。在胰腺癌的体外和体内研究中，EGFR的抑制与抗肿瘤作用相关。我们以前曾报道的EGFR相关蛋白（ERRP），这似乎是一个负调节EGFR的分离和表征。在本研究中，我们测试了我们的假设是否重组ERRP可以是一个有效的抑制剂BxPC 3胰腺癌细胞的生长。分别使用3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四唑和凋亡ELISA测定法在存在和不存在重组ERRP的BxPC 3细胞中测量细胞生长和凋亡。为了评估EGFR及其下游信号传导事件的活化，通过蛋白质印迹分析测定磷酸-EGFR、磷酸-AKT和磷酸-细胞外信号调节激酶（磷酸-ERK）的水平。通过电泳迁移率变动分析测量NF-κ B活性。我们的数据首次表明，ERRP以剂量和时间依赖性方式抑制BxPC3细胞的生长。EGF或转化生长因子（TGF）-α诱导的细胞生长刺激和EGFR活化也被ERRP抑制。这些变化伴随着丝裂原活化蛋白（MAP）激酶、AKT和NF-κ B的活化的伴随衰减。ERRP也诱导细胞凋亡，证明了增加聚（ADP-核糖）聚合酶裂解和减少前半胱氨酸蛋白酶3。从这些结果中，我们得出结论，ERRP是BxPC-3胰腺癌细胞生长的有效抑制剂，这可能是由于EGFR细胞信号传导过程的衰减。我们还认为ERRP可能是胰腺癌的潜在治疗剂。
Dysregulation of the epidermal growth factor receptor (EGFR) signaling network has been frequently reported in pancreatic cancer. Inhibition of EGFR was associated with antitumor effects in both in vitro and in vivo studies of pancreatic cancer. We have previously reported the isolation and characterization of an EGFR-related protein (ERRP), which seems to be a negative regulator of EGFR. In the present investigation, we tested our hypothesis whether recombinant ERRP could be an effective inhibitor of growth of BxPC3 pancreatic cancer cells. Cell growth and apoptosis were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and apoptosis ELISA assay, respectively, in the presence and absence of recombinant ERRP in BxPC3 cells. To evaluate activation of EGFR and its downstream signaling events, levels of phospho-EGFR, phospho-AKT, and phospho-extracellular signal-regulated kinase (phospho-ERK) were determined by Western blot analysis. NF-kappaB activity was measured by electrophoretic mobility shift assay. Our data show, for the first time, that ERRP inhibits the growth of BxPC3 cells in a dose- and time-dependent manner. The EGF or transforming growth factor (TGF)-alpha-induced stimulation of cell growth and activation of EGFR was also inhibited by ERRP. These changes were accompanied by a concomitant attenuation of activation of mitogen-activated protein (MAP) kinases, AKT, and NF-kappaB. ERRP also induced apoptosis as evidenced by increased poly(ADP-ribose) polymerase cleavage and reduction in procaspase3. From these results, we conclude that ERRP is a potent inhibitor of growth of BxPC-3 pancreatic cancer cells, which could be due to attenuation of EGFR cellular signaling processes. We also suggest that ERRP could be a potential therapeutic agent for pancreatic cancer.