Exogenous expression of Esophagin/SPRR3 attenuates the tumorigenicity of esophageal squamous cell carcinoma cells via promoting apoptosis
Exogenous expression of Esophagin/SPRR3 attenuates the tumorigenicity of esophageal squamous cell carcinoma cells via promoting apoptosis
复制标题
DOI：
10.1002/ijc.23104
复制
发表时间：
2008-01-15
影响因子：
6.4
通讯作者：
Wang, Ming-Rong
中科院分区：
文献类型：
--
作者：
Zhang, Yu;Feng, Yan-Bin;Wang, Ming-Rong
食管/SPRR3是一种角膜包膜结构前体蛋白，在上皮细胞分化过程中表达。1996年，另一个研究小组发现，我们自己的实验室随后证实，食管鳞状细胞癌（ESCC）中食管/SPRR3表达频繁且显著降低。然而，食管/SPRR3在食管上皮肿瘤发生中的作用仍未确定。在这项研究中，我们发现食管素/SPRR3在ESCC中经常下调表达。相反，食管素/SPRR3表达下调与临床病理特征无相关性。食管蛋白/SPRR3在发育不良的上皮中表达减少，提示食管蛋白/SPRR3的改变可能是食管鳞状癌发生的早期事件。外源性表达食管素/SPRR3显著抑制ESCC细胞在塑料和软琼脂中形成菌落的能力，以及体内肿瘤的形成。末端脱氧核苷酸转移酶介导的dUTP镍端标记试验和Caspase S活性形式的免疫荧光分析表明，细胞凋亡失调可能有助于降低致瘤性。特别是，在表达食管/SPRR3的ESCC细胞中观察到CDK11p46蛋白的上调，而在对照细胞中则没有，这表明食管/SPRR3诱导的细胞凋亡可能至少部分是由于CDK11p46蛋白的表达增加。这些结果提示，食管/SPRR3可能在维持食管上皮正常稳态中发挥作用，食管/SPRR3的异常表达可能参与ESCC的肿瘤发生。(C) 2007 Wiley-Liss, Inc。
Esophagin/SPRR3 is one of the cornified-envelope structural precursor proteins, which is expressed during epithelia cell differentiation. In 1996, another research group discovered, and our own laboratory subsequently confirmed, frequent and dramatic decreased Esophagin/SPRR3 expression in esophageal squamous cell carcinoma (ESCC). However, the role of Esophagin/SPRR3 in tumorigenesis of esophageal epithelium remains undetermined. In this study, we demonstrate that expression of Esophagin/SPRR3 is frequently downregulated in ESCC. In contrast, no correlations between downregulation of Esophagin/SPRR3 expression and clinicopathologic characteristics were observed. Diminished Esopbagin/SPRR3 expression was present in dysplastic epithelia, suggesting that Esophagin/SPRR3 alteration could represent an early event in squamous carcinogenesis of the esophagus. Exogenous expression of Esophagin/SPRR3 significantly suppressed the ability of ESCC cells to form colonies in plastic and soft agar, as well as tumor formation in vivo. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end label assay and immunofluorescence analysis of the active form of Caspase S indicated that dysregulated apoptosis might contribute to reduced tumorigenicity. In particular, upregulation of CDK11p46 protein was observed in ESCC cells expressing Esophagin/SPRR3, but not in control cells, indicating that Esophagin/SPRR3-induced apoptosis may be due, at least in part, to increased expression of CDK11p46 protein. These findings suggest that Esophagin/SPRR3 may play a role in the maintenance of normal esophageal epithelial homeostasis, and that aberrant expression of Esophagin/SPRR3 may contribute to the tumorigenesis of ESCC. (C) 2007 Wiley-Liss, Inc.