School of Medicine, Griffith University, Gold Coast, Queensland, Australia.
Department of Histopathology, School of Medical Science, Griffith University, Gold Coast, Queensland, Australia.
Mol Carcinog. 2019 Jul;58(7):1145-1154. doi: 10.1002/mc.22998. Epub 2019 Mar 1.
Gene amplified in esophageal cancer 1 (GAEC1) expression and copy number changes are frequently associated with the pathogenesis of colorectal carcinomas. The current study aimed to identify the pathway and its transcriptional factors with which GAEC1 interacts within colorectal cancer, to gain a better understanding of the mechanics by which this gene exercises its effect on colorectal cancer. Two colonic adenocarcinoma cell lines (SW48 and SW480) and a nonneoplastic colon epithelial cell line (FHC) were transfected with GAEC1 to assess the oncogenic potential of GAEC1 overexpression. Multiple in vitro assays, including cell proliferation, wound healing, clonogenic, apoptosis, cell cycle, and extracellular flux, were performed. Western blot analysis was performed to identify potential gene-interaction partners of GAEC1 in vitro. Results showed that the overexpression of GAEC1 significantly increased cell proliferation, migration, and clonogenic potential ( P < 0.05) of colonic adenocarcinoma. Furthermore, GAEC1 portrayed its ability to influence mitochondrial respiration changes. The observations were in tandem with a significant increase in the expression of phosphorylated protein kinase B, forkhead box O3, and matrix metallopeptidase 9. Thus, GAEC1 has a role in regulating gene pathways, potentially in the Akt pathway. This could help in developing targeted therapies in the future.
食管癌基因扩增 1（GAEC1）的表达和拷贝数变化常与结直肠癌的发病机制有关。本研究旨在鉴定 GAEC1 在结直肠癌细胞内相互作用的途径及其转录因子，以更好地了解该基因对结直肠癌发挥作用的机制。用 GAEC1 转染两种结肠腺癌细胞系（SW48 和 SW480）和一种非肿瘤结肠上皮细胞系（FHC），评估 GAEC1 过表达的致癌潜力。进行了多种体外检测，包括细胞增殖、划痕愈合、集落形成、细胞凋亡、细胞周期和细胞外通量检测。进行 Western blot 分析以鉴定 GAEC1 在体外的潜在基因相互作用伙伴。结果表明，GAEC1 的过表达显著增加了结肠腺癌的细胞增殖、迁移和集落形成能力（P<0.05）。此外，GAEC1 表现出影响线粒体呼吸变化的能力。观察结果与磷酸化蛋白激酶 B、叉头框 O3 和基质金属蛋白酶 9 的表达显著增加一致。因此，GAEC1 在调节基因途径方面发挥作用，可能在 Akt 途径中发挥作用。这有助于未来开发靶向治疗。
