肿瘤蛋白p53调节的凋亡诱导蛋白1的过表达通过PI3K/Akt途径调节乳腺癌细胞的增殖和凋亡。
Overexpression of Tumor Protein p53-regulated Apoptosis-inducing Protein 1 Regulates Proliferation and Apoptosis of Breast Cancer Cells through the PI3K/Akt Pathway.
作者信息
Liang Yueyang, Wang Shushu, Liu Jia
机构信息
Department of Breast Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Breast & Thyroid Surgery, Southwest Hospital, Third Military Medical University(Army Medical University), Chongqing, China.
出版信息
J Breast Cancer. 2019 Jun;22(2):172-184. doi: 10.4048/jbc.2019.22.e21.
PURPOSE
Tumor protein p53-regulated apoptosis-inducing protein 1 (TP53AIP1) functions in various cancers. We studied the effect and molecular mechanism of TP53AIP1 in breast cancer.
METHODS
The degree of correlation between TP53AIP1 expression and overall survival in patients with breast cancer was obtained from the online The Cancer Genome Atlas database. Six of the TP53AIP1 levels in the tumor and adjacent non-tumor tissues randomly selected from 38 breast cancer patients were determined. Transgenic technology was used to enhance the expression of TP53AIP1 in breast cancer cell lines, MDA-MB-415 and MDA-MB-468, and to observe the effects of gene overexpression on the proliferation, cell cycle, and apoptosis of breast cancer cells. The molecular mechanism of association between cell cycle- and apoptosis-related factors and the phosphoinositide 3-kinases/protein kinase B (PI3K/Akt) pathway was also studied.
RESULTS
The messenger RNA and protein expression levels of TP53AIP1 in cancer tissues were significantly lower than those in the control group. TP53AIP1 overexpression inhibits cell viability. The mechanism of TP53AIP1 inhibition of proliferation and growth of breast cancer cells includes cell cycle arrest, apoptosis promotion ( < 0.01), promotion of the expression of cleaved-caspase-3 ( < 0.01), cleaved-caspase-9 ( < 0.01), B cell lymphoma/leukemia-2 (Bcl-2)-associated X protein, and p53 ( < 0.01), and the inhibition of Bcl-2, Ki67, and PI3K/Akt pathways ( < 0.01).
CONCLUSION
TP53AIP1 may be a novel tumor suppressor gene in breast cancer and can potentially be used as an effective target gene for the treatment of breast cancer.
目的
肿瘤蛋白p53调节的凋亡诱导蛋白1（TP53AIP1）在多种癌症中发挥作用。我们研究了TP53AIP1在乳腺癌中的作用及分子机制。
方法
从在线的癌症基因组图谱数据库中获取TP53AIP1表达与乳腺癌患者总生存期之间的相关性程度。测定了从38例乳腺癌患者中随机选取的肿瘤组织和相邻非肿瘤组织中TP53AIP1的水平。利用转基因技术增强乳腺癌细胞系MDA-MB-415和MDA-MB-468中TP53AIP1的表达，并观察基因过表达对乳腺癌细胞增殖、细胞周期和凋亡的影响。还研究了细胞周期和凋亡相关因子与磷酸肌醇3激酶/蛋白激酶B（PI3K/Akt）通路之间关联的分子机制。
结果
癌组织中TP53AIP1的信使核糖核酸和蛋白表达水平显著低于对照组。TP53AIP1过表达抑制细胞活力。TP53AIP1抑制乳腺癌细胞增殖和生长的机制包括细胞周期阻滞、促进凋亡（<0.01）、促进裂解的半胱天冬酶-3（<0.01）、裂解的半胱天冬酶-9（<0.01）、B细胞淋巴瘤/白血病-2（Bcl-2）相关X蛋白和p53（<0.01）的表达，以及抑制Bcl-2、Ki67和PI3K/Akt通路（<0.01）。
结论
TP53AIP1可能是乳腺癌中的一种新型抑癌基因，有潜力作为治疗乳腺癌的有效靶基因。
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