Yang Zhenhua, Liu Ying, Shi Changzheng, Zhang Yuqin, Lv Rongzhao, Zhang Rong, Wang Qian, Wang Yiming
Department of Oncology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, P.R. China.
Medical Imaging Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, P.R. China.
Oncol Rep. 2017 Feb;37(2):1011-1019. doi: 10.3892/or.2017.5358. Epub 2017 Jan 9.
The aim of the present study was to evaluate the effects of PTEN/AKT signaling on TUBB3 and TOP2A expression and on the subsequent cell growth of human breast cancer MCF-7 cells. We found that the disease-free survival (DFS) and overall survival (OS) of breast cancer patients with TUBB3‑positive tumors were lower than these rates in the patients with TUBB3-negative tumors. Meanwhile, DFS and OS of breast cancer patients with TOP2A-positive tumors were also lower than these rates in patients with TOP2A-negative tumors. Suppression of PTEN reduced the protein expression of TUBB3 and TOP2A in MCF-7 cells. Suppression of PTEN also reduced cell proliferation and induced apoptosis and caspase-3 activity in MCF-7 cells. Moreover, an increase in ATP also reduced TUBB3 and TOP2A protein expression, reduced cell proliferation and induced apoptosis and caspase-3 activity in the MCF-7 cells following suppression of PTEN. Suppression of phosphorylation-AKT (p-AKT) reduced the protein expression of TUBB3 and TOP2A in the MCF-7 cells. Suppression of p-AKT also reduced cell proliferation and induced apoptosis and caspase-3 activity in the MCF-7 cells. Then, ATP also reduced TUBB3 and TOP2A protein expression, reduced cell proliferation and induced apoptosis and caspase-3 activity in MCF-7 cells following suppression of p-AKT. These results suggest that PTEN/AKT signaling affects the expression of TUBB3 and TOP2A reducing cell growth and inducing apoptosis of human breast cancer MCF-7 cells through ATP and caspase-3 signaling pathways. TUBB3 and TOP2A may be promising prognostic markers for the efficacy of adjuvant cisplatin-based chemotherapy.
本研究的目的是评估PTEN/AKT信号通路对人乳腺癌MCF-7细胞中TUBB3和TOP2A表达以及后续细胞生长的影响。我们发现，TUBB3阳性肿瘤的乳腺癌患者的无病生存期（DFS）和总生存期（OS）低于TUBB3阴性肿瘤患者。同时，TOP2A阳性肿瘤的乳腺癌患者的DFS和OS也低于TOP2A阴性肿瘤患者。PTEN的抑制降低了MCF-7细胞中TUBB3和TOP2A的蛋白表达。PTEN的抑制还降低了MCF-7细胞的增殖并诱导了凋亡和caspase-3活性。此外，ATP的增加在PTEN抑制后也降低了MCF-7细胞中TUBB3和TOP2A的蛋白表达，降低了细胞增殖并诱导了凋亡和caspase-3活性。磷酸化-AKT（p-AKT）的抑制降低了MCF-7细胞中TUBB3和TOP2A的蛋白表达。p-AKT的抑制还降低了MCF-7细胞的增殖并诱导了凋亡和caspase-3活性。然后，ATP在p-AKT抑制后也降低了MCF-7细胞中TUBB3和TOP2A的蛋白表达，降低了细胞增殖并诱导了凋亡和caspase-3活性。这些结果表明，PTEN/AKT信号通路通过ATP和caspase-3信号通路影响TUBB3和TOP2A的表达，减少人乳腺癌MCF-7细胞的生长并诱导其凋亡。TUBB3和TOP2A可能是基于顺铂辅助化疗疗效的有前景的预后标志物。
