Next Article in Journal
Role of Histamine H3 Receptor Antagonists on Intraocular Pressure Reduction in Rabbit Models of Transient Ocular Hypertension and Glaucoma
Previous Article in Journal
Genome-Wide Detection of Major and Epistatic Effect QTLs for Seed Protein and Oil Content in Soybean Under Multiple Environments Using High-Density Bin Map
Open AccessArticle

Metallothionein 3 Is a Hypoxia-Upregulated Oncogene Enhancing Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells

1
Department of Urology, Chang Gung Memorial Hospital-Linkou, Kwei-Shan, Tao-Yuan 33302, Taiwan
2
Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan
3
Department of Anatomy, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan
4
Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan
5
School of Nursing, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan
6
Department of Medicine, College of Medicine, Chang Gung University, Kwei-Shan, Tao-Yuan 33302, Taiwan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(4), 980; https://doi.org/10.3390/ijms20040980
Received: 27 January 2019 / Revised: 19 February 2019 / Accepted: 20 February 2019 / Published: 23 February 2019
(This article belongs to the Section Molecular Biology)
Metallothioneins have been viewed as modulators in a number of biological regulations regarding cancerous development; however, the function of metallothionein 3 (MT3) in bladder cancer is unexplored. We determined the regulatory mechanisms and potential function of MT3 in bladder carcinoma cells. Real-Time Reverse Transcriptase-Polymerase Chain Reaction (RT-qPCR) assays revealed that TSGH-8301 cells expressed more MT3 levels than RT-4, HT1376, and T24 cells. Immunoblot and RT-qPCR assays showed that arsenic (AS2O3) treatments enhanced the gene expression of MT3. Hypoxia induced HIF-1α, HIF-2α, and MT3 expression; furthermore, HIF-2α-knockdown attenuated hypoxic activation on MT3 expression. Ectopic overexpression of MT3 increased cell proliferation, invasion, and tumorigenesis significantly in T24 and HT1376 cells in vitro and in vivo; however, MT3-knockdown in TSGH-8301 cells had the reverse effect. Moreover, knockdown of MT3 enhanced arsenic-induced apoptosis determined by the Annexin V-FITC apoptosis assay. MT3-overexpression downregulated the gene expressions of N-myc downstream regulated gene 1 (NDRG1), N-myc downstream regulated gene 2 (NDRG2), and the mammary serine protease inhibitor (MASPIN) in HT1376 and T24 cells, whereas MT3-knockdown in TSGH-8301 cells had the opposite effect. The experiments indicated that MT3 is an arsenic- and hypoxia-upregulated oncogene that promotes cell growth and invasion of bladder carcinoma cells via downregulation of NDRG1, NDRG2, and MASPIN expressions. View Full-Text
Keywords: metallothionein 3; bladder; tumorigenesis; NDRG1; MASPIN; hypoxia metallothionein 3; bladder; tumorigenesis; NDRG1; MASPIN; hypoxia
Show Figures

Graphical abstract

MDPI and ACS Style

Tsui, K.-H.; Hou, C.-P.; Chang, K.-S.; Lin, Y.-H.; Feng, T.-H.; Chen, C.-C.; Shin, Y.-S.; Juang, H.-H. Metallothionein 3 Is a Hypoxia-Upregulated Oncogene Enhancing Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells. Int. J. Mol. Sci. 2019, 20, 980.

AMA Style

Tsui K-H, Hou C-P, Chang K-S, Lin Y-H, Feng T-H, Chen C-C, Shin Y-S, Juang H-H. Metallothionein 3 Is a Hypoxia-Upregulated Oncogene Enhancing Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells. International Journal of Molecular Sciences. 2019; 20(4):980.

Chicago/Turabian Style

Tsui, Ke-Hung; Hou, Chen-Pang; Chang, Kang-Shuo; Lin, Yu-Hsiang; Feng, Tsui-Hsia; Chen, Chiu-Chun; Shin, Yi-Syuan; Juang, Horng-Heng. 2019. "Metallothionein 3 Is a Hypoxia-Upregulated Oncogene Enhancing Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells" Int. J. Mol. Sci. 20, no. 4: 980.

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop