Medical Research Center, The Affiliated Hospital, Xinjiang Medical University, Urumqi, 830054, Xinjiang Uygur Autonomous Region, People's Republic of China.
Mol Biol Rep. 2012 May;39(5):5315-21. doi: 10.1007/s11033-011-1330-0. Epub 2011 Dec 14.
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.
p38 丝裂原活化蛋白激酶（MAPK）是 MAPK 家族的成员，最初被发现可被应激刺激、促炎细胞因子和生长因子激活。然而，其在食管鳞状细胞癌（ESCC）发病机制中的作用在很大程度上是未知的，因此我们研究了磷酸化 p38（p-p38）MAPK 在 ESCC 中的作用。首先，在体外细胞系 ECa109 中，p38 的选择性抑制剂 SB203580 可以剂量和时间依赖性地抑制食管癌细胞的生长，这表明 ECa109 细胞的生长和增殖与 p-p38 密切相关。通过对 16 对手术切除的 ESCC 和配对的非肿瘤相邻组织（NAT）的新鲜组织进行 Western blot 分析，我们发现 p-p38 在 NAT 中的表达明显高于 ESCC。此外，通过免疫组织化学对 162 对福尔马林固定石蜡包埋（FFPE）的 ESCC 和 NAT 进行验证，p-p38 的表达得到进一步证实，通过统计学分析得到了相同的趋势结果，即与 ESCC 相比，NAT 中 p-p38 的表达增加（P<0.01），并且 p-p38 的表达与淋巴结转移（P>0.05）和 ESCC 分化程度（P>0.05）无显著相关性。综上所述，我们所有的结果表明 p-p38 在 ESCC 的恶性转化中发挥着关键作用。
