Department of Pathology, Tianjin Union Medical Center, Tianjin, 300121, People's Republic of China.
Nankai University School of Medicine, Nankai University, Tianjin, 300071, People's Republic of China.
Clin Transl Oncol. 2019 Feb;21(2):220-231. doi: 10.1007/s12094-018-1912-6. Epub 2018 Jun 28.
The aim of this study is to explore the roles of β-catenin, decorin, septin-7, and S100A10 expression in colorectal cancer development.
Twenty-five BALB/c mice were divided into five groups; four groups were administrated N,N-dimethylhydrazine for 0, 10, 15, and 20 weeks, and one group was administrated normal saline for 20 weeks. The colons were collected for histopathological analysis. Protein samples prepared from the frozen colon tissues of mice treated with N,N-dimethylhydrazine for the different time points were evaluated using the isobaric tags for relative and absolute quantification (iTRAQ) labeling technique coupled with the 2D liquid chromatography-tandem mass spectrometry analysis. Based on the proteomic analysis results, immunohistochemical staining of β-catenin, decorin, septin-7, and S100A10 was performed in paraffin-embedded mice colorectal tissue, and 53 cases of human hereditary polyposis colorectal cancer samples.
Colorectal cancer was observed in mice treated with N,N-dimethylhydrazine for 20 weeks, and adenomas were observed in mice subjected to the 10-, and 15-week treatments. Seventy-two differentially expressed proteins were involved in the development of cancer as per the iTRAQ and spectrometry analysis. In normal epithelium, adenoma, and cancer from human hereditary polyposis colorectal cancer, S100A10 expression (c2 = 100.989, P = 0.000) was highest in cancer, whereas decorin (c2 = 12.852, P = 0.002) and septin-7 (c2 = 66.519, P = 0.002) expressions were highest in the normal epithelium, which was confirmed via immunohistochemical staining.
The subcellular localization of β-catenin and decorin, septin-7, and S100A10 expressions are associated with the development of colorectal cancer in mice after N,N-dimethylhydrazine treatment and in human hereditary polyposis colorectal cancers.
本研究旨在探讨β-连环蛋白、核心蛋白聚糖、七肽-7 和 S100A10 表达在结直肠癌发生发展中的作用。
25 只 BALB/c 小鼠被分为 5 组；4 组分别给予 N，N-二甲基肼 0、10、15 和 20 周，1 组给予生理盐水 20 周。收集结肠组织进行组织病理学分析。采用同位素标记相对和绝对定量（iTRAQ）标记技术结合二维液相色谱-串联质谱分析，评估经不同时间点 N，N-二甲基肼处理的小鼠冷冻结肠组织的蛋白样品。基于蛋白质组学分析结果，对石蜡包埋的小鼠结直肠组织和 53 例遗传性多发性结肠息肉癌样本进行β-连环蛋白、核心蛋白聚糖、七肽-7 和 S100A10 的免疫组织化学染色。
N，N-二甲基肼处理 20 周的小鼠出现结直肠癌，10 周和 15 周处理的小鼠出现腺瘤。iTRAQ 和光谱分析显示，72 种差异表达蛋白参与癌症的发生发展。在人遗传性多发性结肠息肉癌的正常上皮、腺瘤和癌中，S100A10 表达（c2=100.989，P=0.000）在癌中最高，而核心蛋白聚糖（c2=12.852，P=0.002）和七肽-7（c2=66.519，P=0.002）表达在正常上皮中最高，这通过免疫组织化学染色得到证实。
β-连环蛋白和核心蛋白聚糖、七肽-7、S100A10 的亚细胞定位与 N，N-二甲基肼处理后小鼠结直肠癌的发生发展以及人遗传性多发性结肠息肉癌有关。
