关键词: connexin 26 gap junctions second messengers β‐catenin connexin 26 gap junctions second messengers β‐catenin

来  源:   DOI:10.1002/ags3.12552   PDF(Pubmed)

Abstract:
UNASSIGNED: Connexin is a basic molecule that forms gap junctions and undergoes localization changes to the cytoplasm in association with carcinogenesis. We aimed to investigate and clarify the significance of cytoplasmic Cx26 expression in gastric cancer.
UNASSIGNED: We included 87 patients with intestinal- and mix-type gastric cancer and 111 patients with diffuse type gastric cancer who underwent surgery for gastric cancer between 1999 and 2006. Immunohistochemical staining for Cx26, β-catenin, and Wnt3a was performed and analyses of the relationship to clinicopathological factors were conducted based on the Lauren classification. In an in vitro study, the gastric cancer cell lines MKN7, MKN74, and MKN45 were used to evaluate the proliferative capacity using the water-soluble tetrazolium salt assay through forced expression of Cx26, and the relationship between Cx26 and β-catenin was investigated using proximity ligation assay (PLA) and co-immunoprecipitation. Additionally, functional analysis was performed by Cage analysis.
UNASSIGNED: In this study, high cytoplasmic Cx26 expression was associated with favorable prognosis in intestinal- and mix-type gastric cancer and could be an independent prognostic factor for overall survival. In terms of the mechanism, in in vitro experiments changes in Cx26 localization to the cytoplasm were shown to suppress the change of localization of β-catenin to the nucleus by binding to it in the cytoplasm.
UNASSIGNED: Cytoplasmic Cx26 was found to be a prognostic factor in intestinal- and mix-type gastric cancer. Regarding the mechanism, in vitro studies revealed that cytoplasmic Cx26 inhibits the translocation of β-catenin to the nucleus.
摘要:
连接蛋白是一种基本分子,可形成间隙连接,并在与癌变相关的细胞质中发生定位变化。我们旨在研究和阐明细胞质Cx26表达在胃癌中的意义。
我们纳入了在1999年至2006年期间接受胃癌手术的87例肠和混合型胃癌患者和111例弥漫型胃癌患者。Cx26,β-catenin,和Wnt3a进行,并根据Lauren分类进行与临床病理因素的关系分析。在一项体外研究中,使用胃癌细胞系MKN7,MKN74和MKN45,通过Cx26的强制表达,使用水溶性四唑盐测定法评估其增殖能力,并使用邻近连接测定法(PLA)和免疫共沉淀法研究Cx26与β-catenin之间的关系.此外,通过Cage分析进行功能分析。
在这项研究中,在肠型和混合型胃癌中,细胞质Cx26的高表达与良好预后相关,并且可能是总生存期的独立预后因素.在机制方面,在体外实验中,Cx26在细胞质中的定位变化被证明可以通过与细胞质中的β-catenin结合来抑制β-catenin在细胞核中的定位变化。
发现细胞质Cx26是肠型和混合型胃癌的预后因素。关于机制,体外研究表明,细胞质Cx26抑制β-catenin向细胞核的易位。
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