Clinicopathological significance of p38β, p38γ, and p38δ and its biological roles in esophageal squamous cell carcinoma
Clinicopathological significance of p38β, p38γ, and p38δ and its biological roles in esophageal squamous cell carcinoma
复制标题
p38β、p38γ 和 p38γ 的临床病理意义及其在食管鳞状细胞癌中的生物学作用
DOI：
10.1007/s13277-015-4610-9
复制
发表时间：
2016-06-01
期刊：
影响因子：
--
通讯作者：
Lu, Xiaomei
中科院分区：
文献类型：
--
作者：
Zheng, Shutao;Yang, Chenchen;Lu, Xiaomei
与p38 α亚型相比，p38 β、p38 γ和p38 δ已经零星地且几乎没有报道参与癌症的致癌作用。然而，关于它们在食管鳞状细胞癌（ESCC）中的临床病理学意义和生物学作用知之甚少。采用免疫组化技术结合食管鳞癌组织芯片检测p38 β、p38 γ和p38 δ的表达情况，并对临床病理意义进行统计学分析。采用MTT法、创伤愈合实验和Transwell实验研究其对食管鳞癌细胞系Eca109增殖、迁移和侵袭的影响。作为确认，取无胸腺裸鼠以验证对体内增殖的影响。结果发现，除了p38 γ，p38 β和p38 δ的表达在ESCC组织中显著高于配对的正常对照。在预后方面，仅观察到p38 β表达与总体预后显著相关。在临床病理学上，p38 γ表达与临床分期、淋巴结转移和肿瘤体积有显著相关性。p38 β和p38 δ在食管鳞癌中的表达与其他临床病理参数无显著相关性，但在正常对照组中的表达有显著性差异。在Eca109中，观察到p38 β、p38 γ和p38 δ可以促进细胞生长和运动。作为验证，p38 δ的过表达可以促进，而p38 γ的敲低可以防止，在用Eca109细胞异种移植的裸鼠模型中的肿瘤发生，Eca109细胞的p38 δ的基础水平稳定地过表达并且p38 γ被稳定地敲低。总之，我们的研究结果表明，p38 β，p38 γ和p38 δ在ESCC中发挥致癌作用。
P38 beta, p38 gamma, and p38 delta have been sporadically and scarcely reported to be involved in the carcinogenesis of cancers, compared with p38 alpha isoform. However, little has been known regarding their clinicopathological significance and biological roles in esophageal squamous cell carcinoma (ESCC). Expression status of p38 beta, p38 gamma, and p38 delta was assayed using immunohistochemistry with ESCC tissue microarray; ensuing clinicopathological significance was statistically analyzed. To define its biological roles on proliferation, migration and invasion of ESCC cell line Eca109 in vitro, MTT, wound healing, and Transwell assays were employed, respectively. As confirmation, athymic nude mice were taken to verify the effect over proliferation in vivo. It was found that both p38 beta and p38 delta expression, other than p38 gamma, were significantly higher in ESCC tissues compared with paired normal controls. In terms of prognosis, only p38 beta expression was observed to be significantly associated with overall prognosis. Clinicopathologically, there was significant association between p38 gamma expression and clinical stage, lymph nodes metastases, and tumor volume. No significant association was found for p38 beta and p38 delta between its expression and other clinicopathological parameters other than significant difference of expression between ESCC versus normal control. In Eca109, it was observed that p38 beta, p38 gamma, and p38 delta can promote the cell growth and motility. As verification, over-expression of p38 delta can promote, whereas knockdown of p38 gamma can prevent, the tumorigenesis in nude mice model xenografted with Eca109 cells whose basal level of p38 delta was stably over-expressed and p38 gamma was stably knocked down. Together, our results demonstrate that p38 beta, p38 gamma, and p38 delta played oncogenic roles in ESCC.