Department of Biochemistry, Dong-A University College of Medicine, Busan, Republic of Korea.
Department of Biochemistry, Dong-A University College of Medicine, Busan, Republic of Korea
Anticancer Res. 2020 Feb;40(2):767-777. doi: 10.21873/anticanres.14008.
BACKGROUND/AIM: Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) plays an important role in cancer. We examined the effect of COUP-TFII overexpression on the proliferation and invasion of the human colorectal cancer SNU-C4 cells.
SNU-C4 cells were stably transfected with COUP-TFII expression plasmid to overexpress COUP-TFII (COUP-TFII-SNU-C4 cells). Cell proliferation, colony-forming ability and transwell invasion assays were performed. To elucidate the underlying molecular mechanism of COUP-TFII action, western blot analysis, p53 shRNA transfection, and Myr-Akt transfection were performed.
Cell proliferation and colony-forming ability were significantly inhibited in COUP-TFII-SNU-C4 cells. Western blot analyses demonstrated that while the expression of p53 and PTEN was increased, the p-Akt levels were decreased in COUP-TFII-SNU-C4 cells. Knockdown of p53 partially restored the cell proliferation, but did not reverse the inhibition of invasion. Constitutive activation of Akt via Myr-Akt transfection reversed the inhibited cell proliferation and invasion by COUP-TFII.
p53 is required for the inhibition of cell proliferation, and decreased phosphorylation of Akt may mediate the inhibition of cell proliferation and invasion by COUP-TFII.
背景/目的：鸡卵清蛋白上游启动子转录因子 II（COUP-TFII）在癌症中发挥重要作用。我们研究了过表达 COUP-TFII 对人结直肠癌细胞 SNU-C4 增殖和侵袭的影响。
用 COUP-TFII 表达质粒稳定转染 SNU-C4 细胞以过表达 COUP-TFII（COUP-TFII-SNU-C4 细胞）。进行细胞增殖、集落形成能力和 Transwell 侵袭实验。为阐明 COUP-TFII 作用的潜在分子机制，进行了 Western blot 分析、p53 shRNA 转染和 Myr-Akt 转染。
COUP-TFII-SNU-C4 细胞的细胞增殖和集落形成能力显著受到抑制。Western blot 分析表明，COUP-TFII-SNU-C4 细胞中 p53 和 PTEN 的表达增加，而 p-Akt 水平降低。p53 的敲低部分恢复了细胞增殖，但未逆转侵袭的抑制。通过 Myr-Akt 转染使 Akt 持续激活逆转了 COUP-TFII 对细胞增殖和侵袭的抑制作用。
p53 是抑制细胞增殖所必需的，而 Akt 的磷酸化减少可能介导了 COUP-TFII 对细胞增殖和侵袭的抑制作用。
