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ToxSci Advance Access published online on March 23, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi155
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Toxicological Sciences © 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 January 19, 2005
Accepted March 17, 2005

Environmental Toxicology

Post-Transcriptional Regulation of Metallothionein Isoform 1 and 2 Expression in the Human Breast and the MCF-10A Cell Line

Volkan Gurel 1, Donald A. Sens 2, Seema Somji 1, Scott H. Garrett 1, Tim Weiland 1, and Mary Ann Sens 1*

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.
Mary Ann Sens, E-mail: msens{at}medicine.nodak.edu


  Abstract

Studies have shown using immunohistochemical staining that the MT-1 and MT-2 proteins (MT-1/2) are overexpressed in a substantial sub-set of ductal breast cancers, that overexpression occurs early in the disease process, and is indicative of a poor prognosis. Normal ductal breast epithelium fails to immunostain for the MT-1/2 protein where as the myoepithelial cells of the ducts stain intensely. There is no information regarding the expression of the mRNAs for the 8 active MT-1 and MT-2 genes in normal breast duct epithelium. Microdissection of normal breast samples was used to obtain total RNA from enriched populations of ductal epithelium and myoepithelium. Analysis by RT-PCR demonstrated that the identity of the MT isoform-specific genes expressed (MT-2A and MT-1X) and their relative levels of expression were similar between the myoepithelial and ductal components. These findings indicate that the ductal and myoepithelial components express similar amounts of MT-2A and MT-1X mRNAs, but have distinctly different expression of the MT-1/2 protein. Confluent cultures of MCF-10A breast epithelial cells were exposed to Cd+2 to test for evidence of post-transcriptional regulation of MT-1/2 protein accumulation in ductal epithelium. It was demonstrated that Cd+2 elicited only a marginal induction of MT-1E, MT-1X or MT-2A mRNAs; where as, there was a marked increase in MT-1/2 protein, reaching levels of 6% of total cell protein under conditions of extended exposure. This study suggests that the mechanism underlying the finding of increased MT-1/2 protein expression in ductal breast cancer may involve in part the post-transcriptional regulation of MT-1/2 protein expression.

Keywords: Metallothionein; Breast Cancer; Cadmium; MCF-10A; Ductal Epithelium; Myoepithelium; Microdissection.
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