Skip Navigation



ToxSci Advance Access published online on June 15, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi231
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
87/1/66    most recent
kfi231v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Garrett, S. H.
Right arrow Articles by Sens, D. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Garrett, S. H.
Right arrow Articles by Sens, D. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received April 26, 2005
Accepted June 10, 2005

Environmental Toxicology

Expression of Metallothoinein Isoform 3 is Restricted at the Post-Transcriptional Level in Human Bladder Epithelial Cells

Scott H. Garrett 1, Seongmi Park 1, Mary Ann Sens 1, Seema Somji 1, Rajendra K. Singh 1, Venugopal BRK Namburi 1, and Donald A. Sens 2*

1 Department of Pathology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58202
2 Department of Surgery, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58202

* To whom correspondence should be addressed.
Donald A. Sens, E-mail: dsens{at}medicine.nodak.edu


  Abstract

This study was designed to define the effect that overexpression of MT-3 would have on a cell culture model of bladder urothelium. Stable and inducible transfection was used to achieve overexpression of the MT-3 gene in the UROtsa cell line. When the UROtsa cells were stably transfected with the MT-3 coding sequence, there was highly elevated expression of MT-3 mRNA, but no MT-3 protein. An inducible vector showed that low basal levels of MT-3 mRNA and protein could be produced, but that induction only increased MT-3 mRNA and not protein. The clones expressing low basal levels of MT-3 protein also had reduced growth rates compared to control cells. Site directed mutagenesis was used to produce an MT-3 coding sequence where the prolines in positions 7 and 9 were converted to threonines. When this altered MT-3 was stably transfected into the UROtsa cells, the cells were able to accumulate the mutated form of the MT-3 protein. These studies show that MT-3 protein expression is inhibited by post transcriptional control in the urothelial cell. Modifying the MT-3 protein to resemble the MT-1 isoform removes this component of post transcriptional control and allows accumulation of the mutated MT-3 protein. The altered sequence involved in post transcriptional control of MT-3 protein expression is the same sequence implicated in the neuronal growth inhibitory activity associated specifically with the MT-3 isoform of the MT gene family.

Keywords: Metallothionein; Bladder Cancer; Cadmium; Urothelium; UROtsa; Post Transcriptional Control; Growth Inhibitory Factor.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
X. D. Zhou, M. A. Sens, S. H. Garrett, S. Somji, S. Park, V. Gurel, and D. A. Sens
Enhanced Expression of Metallothionein Isoform 3 Protein in Tumor Heterotransplants Derived from As+3- and Cd+2-Transformed Human Urothelial Cells
Toxicol. Sci., October 1, 2006; 93(2): 322 - 330.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
S. Somji, S. H. Garrett, M. A. Sens, and D. A. Sens
The Unique N-Terminal Sequence of Metallothionein-3 Is Required to Regulate the Choice between Apoptotic or Necrotic Cell Death of Human Proximal Tubule Cells Exposed to Cd+2
Toxicol. Sci., April 1, 2006; 90(2): 369 - 376.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.