Abstract
TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and related halogenated aromatic hydrocarbons elicit a diverse spectrum of biochemical and toxic responses in laboratory animals and mammalian cells in culture. Toxicity and carcinogenicity of TCDD is well established but the molecular mechanism is still poorly understood. Here, we found the noble responsive genes to TCDD using the differential display analysis. Treatment of HepG2 cells with TCDD showed a significantly different mRNA expression pattern from the untreated cells in differential display analysis. The differentially displayed bands were isolated and used as probes in dot blot and Northern blot analyses. Of thirty-five isolated differentially displayed bands, only two bands were confirmed as positive in dot blot and Northern blot analyses. The nucleotides sequences of these clones were analyzed and the search of Genebank database revealed that one clone is highly homologous with RanBP2 (Ras-related nuclear protein binding protein2; 92%) and the other is an unknown gene. RanBP2 is a nucleoporin with SUMO E3 ligase activity that functions in both nucleocytoplasmic transport and mitosis and its role as a novel tumor suppressor has been recently proposed. Thus, these results may suggest the clue elucidating the toxic mechanism of TCDD through RanBP2.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Cho, Y.-J. Meade J.D., Walden, J.C., Chen, X., Guo, Z. and Liang, P. (2001). Multicolor fluorescent differential display. BioTechniques, 30, 562–572.
Dawlaty, M.M., Malureanu, L., Jeganathan, K.B., Kao, E., Sustmann, C., Tahk, S., Shuai, K., Grosschedl, R. and van Deursen, J.M. (2008). Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase IIalpha. Cell, 133, 103–115.
Fingerhut, M.A., Halperin, W.E., Marlow, D.A., Piacitelli, L.A., Honchar, P.A., Sweeney, M.H., Greife, A.L., Dill, P.A., Steenland, K. and Suruda, A.J. (1991). Cancer mortality in workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. N. Engl. J. Med., 324, 212–218.
Flesch-Janys, D., Berger, J., Gurn, P., Manz, A., Nagel, S., Waltsgott, H. and Dwyer, J.H. (1995). Exposure to polychlorinated dioxins and furans (PCDD/F) and mortality in a cohort of workers from a herbicide-producing plant in Hamburg, Federal Republic of Germany. Am. J. Epidemiol., 142, 1165–1175.
Gasiewicz, T.A., Henry, E.C. and Collins, L.L. (2008). Expression and activity of aryl hydrocarbon receptors in development and cancer. Crit. Rev. Eukaryot. Gene Expr., 18, 279–321.
Geiger, L.E. and Neal, R.A. (1981). Mutagenicity testing of 2,3,7,8-tetrachlordibenzo-p-dioxin in histidine auxotrophs of Salmonella typhimurium. Toxicol. Appl. Pharmacol., 59, 125–129.
Haque, M., Francis, J. and Sehgal, I. (2005). Aryl hydrocarbon exposure induces expression of MMP-9 in human prostate cancer cell lines. Cancer Lett., 225, 159–166.
Kester, H.A., van der Leede, B.M., van der Saag, P.T. and van der Burg, B. (1997). Novel progesterone target genes identified by an improved differential display technique suggest that progestin-induced growth inhibition of breast cancer cells coincides with enhancement of differentiation. J. Biol. Chem., 272, 16637–16643.
Knutson, J.C. and Poland, A. (1982). Response of murine epidermis to 2,3,7,8-tetrachlorodibenzo-p-dioxin: interaction of the ah and hr loci. Cell, 30, 225–234.
Kociba, R.J., Keyes, D.G., Beyer, J.E., Carreon, R.M., Wade, C.E., Dittenber, D.A., Kalnins, R.P., Frauson, L.E., Park, C.N., Barnard, S.D., Hummel, R.A. and Humiston, C.G. (1978). Results of a two-year chronic toxicity and oncogenicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. Toxicol. Appl. Pharmacol., 46, 279–303.
Kohle, C., Schwarz, M. and Bock, K.W. (2008). Promotion of hepatocarcinogenesis in humans and animal models. Arch. Toxicol., 82, 623–631.
Liang, P. (2006). From differential display to DNA microarrays— a personal account. J. Cell Physiol., 209, 653–658.
Liang, P., Averboukh, L. and Pardee, A.B. (1993). Distribution and cloning of eukaryotic mRNAs by means of differential display: refinements and optimization. Nucleic Acids Res., 21, 3269–3275.
Liang, P. and Pardee, A.B. (1992). Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science, 257, 967–971.
Manz, A., Berger, J., Dwyer, J.H., Flesch- Janys, D., Nagel, S. and Waltsgott, H. (1991). Cancer mortality among workers in chemical plant contaminated with dioxin. Lancet, 338, 959–964.
Mukerjee, D. (1998). Health impact of polychlorinated dibenzop-dioxins: a critical review. J. Air. Waste Manag. Assoc., 48, 157–165.
Navarro, M.S. and Bachant, J. (2008). RanBP2: a tumor suppressor with a new twist on TopoII, SUMO, and centromeres. Cancer Cell, 13, 293–295.
Neal, R.A., Olson, J.R., Gasiewicz, T.A. and Geiger, L.E. (1982). The toxicokinetics of 2,3,7,8-tetrachlorodibenzo-pdioxin in mammalian systems. Drug Metab. Rev., 13, 355–385.
Nebert, D.W., Petersen, D.D. and Fornace, A.J. Jr. (1990). Cellular responses to oxidative stress: the [Ah] gene battery as a paradigm. Environ. Health Perspect., 88, 13–25.
Pichler, A., Gast, A., Seeler, J.S., Dejean, A. and Melchior, F. (2002). The nucleoporin RanBP2 has SUMO1 E3 ligase activity. Cell, 108, 109–120.
Poland, A. and Knutson, J.C. (1982). 2,3,7,8-tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity. Annu. Rev. Pharmacol. Toxicol., 22, 517–554.
Raunio, H. and Pelkonen, O. (1983). Effect of polycyclic aromatic compounds and phorbol esters on ornithine decarboxylase and aryl hydrocarbon hydroxylase activities in mouse liver. Cancer Res., 43, 782–786.
Reyes, H., Reisz-Porszasz, S. and Hankinson, O. (1992). Identification of the Ah receptor nuclear translocator protein (Arnt) as a component of the DNA binding form of the Ah receptor. Science, 256, 1193–1195.
Stein, J. and Liang, P. (2002). Differential display technology: a general guide. Cell Mol. Life Sci., 59, 1235–1240.
Stein, S. and Liang, P. (2002). Differential display analysis of gene expression in mammals: a p53 story. Cell Mol. Life Sci., 59, 1274–1279.
Suskind, R.R. (1985). Chloracne, “the hallmark of dioxin intoxication”. Scand. J. Work Environ. Health, 11, 165–171.
Vogeli-Lange, R., Burckert, N., Boller, T. and Wiemken, A. (1996). Rapid selection and classification of positive clones generated by mRNA differential display. Nucleic Acids Res., 24, 1385–1386.
Yokoyama, N., Hayashi, N., Seki, T., Pante, N., Ohba, T., Nishii, K., Kuma, K., Hayashida, T., Miyata, T., Aebi, U., Fukui, M. and Nishimoto, T. (1995). A giant nucleopore protein that binds Ran/TC4. Nature, 376, 184–188.
Zugerman, C. (1990). Chloracne. Clinical manifestations and etiology. Dermatol. Clin., 8, 209–213.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Kim, D., Lim, YR., Park, HG. et al. Differential Display Analysis of 2,3,7,8-Tetrachlorodibenzo-p-dioxin Identified Induction of Ras-related Nuclear Protein Binding Protein2 (RanBP2) Gene. Toxicol Res. 25, 35–40 (2009). https://doi.org/10.5487/TR.2009.25.1.035
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.5487/TR.2009.25.1.035