Amyloid precursor protein is overexpressed in bladder cancer and contributes to the malignant bladder cancer cell behaviors

作者：Zhang, Dongqing; Zhou, Changkuo; Li, Yan; Gao, Lijian; Pang, Zhipeng; Yin, Gang; Shi, Benkang^*

来源：International Journal of Urology, 2018, 25(9): 808-816.

DOI：10.1111/iju.13726

• amyloid precursor protein
• bladder cancer
• cell cycle
• cell proliferation
• extracellular signal-regulated protein kinases pathway

ObjectivesTo investigate the expression of amyloid precursor protein in bladder cancer, and to study its role in malignant bladder cancer cell behaviors.
MethodsImmunohistochemistry and western blotting analysis were used to detect the amyloid precursor protein level in bladder cancer tissues and cell lines. The effect of amyloid precursor protein on bladder cancer cell proliferation, migration, invasion and cell cycle was evaluated by using small interfering ribonucleic acid. The levels of RAS, RAF, MEK, phosphorylated MEK, extracellular regulated protein kinases, phosphorylated extracellular regulated protein kinases, protein kinase B and phosphorylated protein kinase B were determined by western blot after amyloid precursor protein knockdown. The effect of amyloid precursor protein on the extracellular regulated protein kinases pathway was further evaluated using extracellular regulated protein kinases pathway agonist, ceramide C6.
ResultsThe expression of amyloid precursor protein was significantly increased in the human bladder cancer tissues compared with matched normal bladder tissues. The overexpression of amyloid precursor protein was significantly associated with tumor stage, tumor size, histological grade and lymph node metastasis. The proliferation, migration and invasion of human bladder cancer cells were significantly inhibited by the silencing of amyloid precursor protein. In addition, knockdown of amyloid precursor protein arrested the cell cycle progression of bladder cancer cells in the G2/M phase. Mechanistic analysis showed that knockdown of amyloid precursor protein significantly decreased the phosphorylation of extracellular regulated protein kinases. Ceramide C6 could rescue the malignant bladder cancer cell behaviors inhibited by the silencing of amyloid precursor protein.
ConclusionsAmyloid precursor protein is upregulated in bladder cancer, and might be closely associated with bladder cancer cell growth and survival. Amyloid precursor protein could potentially be used as a therapeutic target for bladder cancer treatment.

• 出版日期2018-9
• 单位山东大学