Skip Navigation



ToxSci Advance Access published online on May 28, 2003

Toxicological Sciences, doi:10.1093/toxsci/kfg124
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
74/1/32    most recent
kfg124v1
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 Bae, D.-S.
Right arrow Articles by Campain, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bae, D.-S.
Right arrow Articles by Campain, J. A.
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received January 27, 2003; accepted April 17, 2003
© 2003 Society of Toxicology

Carcinogenicity

Gene Expression Patterns as Potential Molecular Biomarkers for Malignant Transformation in Human Keratinocytes Treated with MNNG, Arsenic, or a Metal Mixture

Dong-Soon Bae 1, Robert J. Handa 2, Raymond S. H. Yang 1, Julie A. Campain 1*

1 Quantitative and Computational Toxicology Group, Center for Environmental Toxicology and Technology, Department of Environmental and Radiological Sciences, Colorado State University, Fort Collins, Colorado 80523
2 Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523

* To whom correspondence should be addressed. E-mail: julie.campain{at}colostate.edu.


   Abstract

In previous studies, treatment with MNNG enhanced malignant transformation of RHEK-1 keratinocytes. In contrast, As alone or in a mixture of As, Cd, Cr, and Pb inhibited this process. Microarray analysis showed unique gene expression patterns in RHEK-1 exposed to MNNG, As, or the metal mixture. From this analysis, we have selected 16 genes potentially involved in the enhancement or inhibition of transformation. These 16 genes, 9 (IFN inducible protein 9-27, MAA A32, CCLB protein, integrin {beta}4, XRCC1, K8, K18, MT3, MAPKK6) of which were altered in a chemical-specific manner and 7 (MIC1, bikunin, MTS1, BMP4, RAD23A, DOC2, vimentin) which were commonly affected by the MNNG and As or mixture treatments, were examined for expression in detail by Real Time RT-PCR. Qualitatively, both microarray and Real Time PCR analyses gave comparable results for 15 of 16 genes, i.e. genes were consistently induced or suppressed under the different treatment regimens when measured by either technique. Of the 7 genes altered in their expression by multiple chemical treatments, 5 showed patterns consistent with a role in the transformation process, i.e. they were oppositely regulated in MNNG-transformed RHEK-1 cells (designated as OM3) as compared to the non-malignant As- and mixture-exposed cells. Through time-course studies, we also identified two markers whose expression correlates with acquisition of transformation-associated characteristics in OM3. Identification of a battery of genes altered during progressive transformation of RHEK-1 should aid in a mechanistic understanding of this process, as well as strengthening the utility of these genes as biomarkers.

Key Words: arsenic, metal mixture, gene expression, cDNA microarray, Real Time RT-PCR, human keratinocytes, RHEK-1 cells .


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
Cancer Epidemiol. Biomarkers Prev.Home page
M. Argos, M. G. Kibriya, F. Parvez, F. Jasmine, M. Rakibuz-Zaman, and H. Ahsan
Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a bangladeshi population.
Cancer Epidemiol. Biomarkers Prev., July 1, 2006; 15(7): 1367 - 1375.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
D. Talantov, A. Mazumder, J. X. Yu, T. Briggs, Y. Jiang, J. Backus, D. Atkins, and Y. Wang
Novel Genes Associated with Malignant Melanoma but not Benign Melanocytic Lesions
Clin. Cancer Res., October 15, 2005; 11(20): 7234 - 7242.
[Abstract] [Full Text] [PDF]


Home page
Toxicol PatholHome page
Xing Cui, Song Li, A. Shraim, Y. Kobayashi, T. Hayakawa, S. Kanno, M. Yamamoto, and S. Hirano
Subchronic Exposure to Arsenic Through Drinking Water Alters Expression of Cancer-Related Genes in Rat Liver
Toxicol Pathol, January 1, 2004; 32(1): 64 - 72.
[Abstract] [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.