The status of phosphorylated p38 in esophageal squamous cell carcinoma
The status of phosphorylated p38 in esophageal squamous cell carcinoma
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食管鳞癌中磷酸化p38的状态
DOI：
10.1007/s11033-011-1330-0
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发表时间：
2012-05-01
影响因子：
2.8
通讯作者：
Lu, Xiao-mei
中科院分区：
文献类型：
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作者：
Zheng, Shu-tao;Zhang, Chuan-shan;Lu, Xiao-mei
p38丝裂原活化蛋白激酶（MAPK）是MAPK家族的成员，其最初被发现被应激刺激、促炎细胞因子和生长因子激活。然而，它在食管鳞状细胞癌（ESCC）的发病机制中的作用在很大程度上是未知的，所以我们研究磷酸化p38（p-p38）MAPK在ESCC中的作用。首先，体外实验表明，选择性p38抑制剂SB 203580对食管癌细胞株ECa 109的生长具有抑制作用，且呈剂量和时间依赖性，提示p-p38与ECa 109细胞的生长增殖密切相关。使用蛋白质印迹分析新鲜的16对手术切除的ESCC和匹配的非肿瘤邻近组织（NAT），我们发现，p-p38在NAT中的表达显着高于ESCC。进一步用免疫组化方法对162对福尔马林固定石蜡包埋（FFPE）的食管鳞癌和NAT进行了p-p38表达的进一步证实，统计学分析得到了与食管鳞癌相比，NAT中p-p38表达增加的趋势相同的结果p-p38的表达与食管鳞癌的淋巴结转移（P> 0.05）、分化程度（P> 0.05）无关。综上所述，我们获得的所有结果表明，p-p38在ESCC的恶性转化中起着关键作用。
The p38 mitogen-activated protein kinase (MAPK) is a member of the MAPK family, which is initially found to be activated by stress stimuli, proinflammatory cytokines, and growth factors. However, its role in the pathogenesis of esophageal squamous cell carcinoma (ESCC) is largely unkown, so we investigate the role of phosphorylated p38 (p-p38) MAPK in ESCC. First of all, in vitro cell line ECa109, SB203580 as selective inhibitor of p38, can suppress the growth of esophageal cancer cell in a dose- and time-dependent way, suggesting that ECa109 cell growth and proliferation was closely associated with p-p38. Using western-blot analysis of fresh 16 paired surgically resected ESCC and matched non-tumor adjacent tissues (NAT), we showed that p-p38 was significantly expressed higher in NAT compared to ESCC. Moreover, expressions of p-p38 were further confirmed by 162 paired of formalin-fixed paraffin-embedded (FFPE) ESCC and NAT by immunohistochemistry, the same trend result was obtained through statistical analysis that there was increased expression of p-p38 in NAT as compared with ESCC (P< 0.01), and expression of p-p38 was not significantly associated with lymph nodes metastasis (P> 0.05) and ESCC differentiation degree (P> 0.05). Taken together, all the results we obtained demonstrated that p-p38 plays a key role in the malignant transformation of ESCC.