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
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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
* To whom correspondence should be addressed. E-mail: julie.campain{at}colostate.edu.
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
© 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
2 Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523
Abstract 
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.
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