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)
  |  
PDF [2109 KB, uploaded 23 February 2019]
  |  

Abstract

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
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

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.

Show more citation formats Show less citations formats

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

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top