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Amyloid precursor protein is overexpressed in bladder cancer and contributes to the malignant bladder cancer cell behaviors
Author(s) -
Zhang Dongqing,
Zhou Changkuo,
Li Yan,
Gao Lijian,
Pang Zhipeng,
Yin Gang,
Shi Benkang
Publication year - 2018
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1111/iju.13726
Subject(s) - amyloid precursor protein , kinase , bladder cancer , cancer research , protein kinase a , cancer cell , cancer , biology , microbiology and biotechnology , medicine , pathology , alzheimer's disease , disease
Objectives To investigate the expression of amyloid precursor protein in bladder cancer, and to study its role in malignant bladder cancer cell behaviors. Methods Immunohistochemistry 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. Results The 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. Conclusions Amyloid 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.