Effects of long term low- and high-dose sodium arsenite exposure in human transitional cells.
Epidemiological studies have revealed the association between increased risk of bladder cancer and chronic arsenic exposure. Here, we explored biological effects of arsenic in T24. Microarray analysis was applied to analyze mRNA in T24 following 0, 2 or 5 μM sodium arsenite (As) exposure for 72 hours. Long term (up to 140 days) low-dose (200 nM) and high-dose (1,000 nM) As decreased E-cadherin protein level through different mechanisms because the mRNA levels of E-cadherin increased following low-dose As exposure but decreased following high-dose As exposure. Long term As increased the protein levels of N-cadherin, vimentin, β-catenin, and slug. Low-dose As exposure resulted in a change in the morphology of T24 cells from an epithelial to a mesenchymal-like appearance. Knockdown of E-cadherin increased the protein levels of N-cadherin, vimentin, β-catenin, and slug. Cell proliferation and growth of T24 with or without As exposure for 100 days were assayed using EdU and WST, respectively. Low-dose As exposure increased cell proliferation and growth while high-dose As exposure decreased both. Long term As activated p53 on account of increasing protein levels of p53, p-p53 (Ser15), and mRNA levels of p21. These demonstrate that arsenic exposure exerts multiple effects. Long term low- or high-dose arsenic induces epithelial-mesenchymal transition, likely via downregulation of E-cadherin, activates p53, and differently affects cell proliferation/growth.
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Daping Hospital, Third Military Medical UniversityChongqing 400042, China; Department of Oncology, Hebei Provincial Hospital of Traditional Chinese MedicineShijiazhuang 050011, Hebei Province, China.
Jianming
J
He
Department of Clinical Laboratory, Institute of Surgery Research, Daping Hospital, Third Military Medical University Chongqing 400042, China.
Feng
F
Wang
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Daping Hospital, Third Military Medical University Chongqing 400042, China.
Fen
F
Luo
Department of Medical Genetics, Third Military Medical University Chongqing 400038, China.
Xuedan
X
Chen
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Daping Hospital, Third Military Medical UniversityChongqing 400042, China; Department of Radiology, Hebei Provincial Hospital of Traditional Chinese MedicineShijiazhuang 050011, Hebei Province, China.
Xi
X
Liang
Department of Clinical Laboratory, Institute of Surgery Research, Daping Hospital, Third Military Medical University Chongqing 400042, China.
Wenbin
W
Jiang
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Daping Hospital, Third Military Medical University Chongqing 400042, China.
Zhizhong
Z
Huang
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Daping Hospital, Third Military Medical University Chongqing 400042, China.
Jiafan
J
Lei
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Daping Hospital, Third Military Medical University Chongqing 400042, China.
Fabo
F
Shan
Molecular Biology Center, State Key Laboratory of Trauma, Burn, and Combined Injury, Daping Hospital, Third Military Medical University Chongqing 400042, China.
Xueqing
X
Xu
Bladder cancer; E-cadherin; arsenic; epithelial-mesenchymal transition; proliferation