Yang Tian-Wen, Gao Yun-Han, Ma Sha-Ying, Wu Qiang, Li Zhong-Fu
Tian-Wen Yang, Department of Gastroenterology, Yongchuan Hospital, Chongqing Medical University, Chongqing 400014, China.
World J Gastroenterol. 2017 May 7;23(17):3066-3076. doi: 10.3748/wjg.v23.i17.3066.
To comparatively investigate the cellular and molecular characteristics of low-grade slightly elevated adenomas and polypoid adenomas.
Colorectal tumors were collected from 24 patients with slightly elevated adenomas and 23 patients with polypoid adenomas. Five commonly mutated genes (, , , , and ) were selected for mutational analysis. Paraffin-embedded tumor sections were used to calculate the apoptotic index (AI) and Ki-67 labeling index (KLI). Two pure colorectal epithelial cell lines were created by pooling the slightly elevated and polypoid tumors. Western blots, luciferase assays for β-catenin-T-cell factor protein/β-catenin-lymphoid enhancer factor (β-catenin-TCF/LEF)-driven transcriptional activity, and caspase activity assays were conducted on the two cell lines.
Slightly elevated lesions showed a significantly lower mutational frequency and a significantly higher mutational frequency (both < 0.05). Slightly elevated lesions showed a significantly lower AI ( < 0.05). β-catenin and β-catenin-TCF/LEF-driven transcriptional activity was significantly upregulated in slightly elevated lesions (both < 0.05). In slightly elevated lesions, c-Myc was significantly downregulated, while cyclin D1 was significantly upregulated (both < 0.05). β-catenin-TCF/LEF-driven transcriptional activity was negatively correlated with c-Myc (ρ = -0.78). Slightly elevated lesions displayed significant Bcl-2 and Bcl-xL upregulation (both < 0.05) along with significant decreases in caspase-9 and caspase-3 activity (both < 0.05). c-Myc was negatively correlated with Bcl-2 and Bcl-xL (ρ = -0.74 and -0.78, respectively).
The lower apoptotic activity of low-grade slightly elevated adenomas can be partly attributed to upregulated β-catenin pathway activity and downregulated c-Myc expression.
比较研究低级别轻度隆起性腺瘤和息肉状腺瘤的细胞及分子特征。
收集24例轻度隆起性腺瘤患者和23例息肉状腺瘤患者的结直肠肿瘤。选择5个常见突变基因（、、、和）进行突变分析。采用石蜡包埋的肿瘤切片计算凋亡指数（AI）和Ki-67标记指数（KLI）。通过汇集轻度隆起性和息肉状肿瘤创建了两种纯结直肠上皮细胞系。对这两种细胞系进行蛋白质免疫印迹分析、β-连环蛋白-T细胞因子蛋白/β-连环蛋白-淋巴增强因子（β-连环蛋白-TCF/LEF）驱动的转录活性荧光素酶测定以及半胱天冬酶活性测定。
轻度隆起性病变显示突变频率显著较低，而突变频率显著较高（均<0.05）。轻度隆起性病变显示AI显著较低（<0.05）。在轻度隆起性病变中，β-连环蛋白和β-连环蛋白-TCF/LEF驱动的转录活性显著上调（均<0.05）。在轻度隆起性病变中，c-Myc显著下调，而细胞周期蛋白D1显著上调（均<0.05）。β-连环蛋白-TCF/LEF驱动的转录活性与c-Myc呈负相关（ρ = -0.78）。轻度隆起性病变显示Bcl-2和Bcl-xL显著上调（均<0.05），同时半胱天冬酶-9和半胱天冬酶-3活性显著降低（均<0.05）。c-Myc与Bcl-2和Bcl-xL呈负相关（ρ分别为-0.74和-0.78）。
低级别轻度隆起性腺瘤较低的凋亡活性可能部分归因于β-连环蛋白通路活性上调和c-Myc表达下调。
