Toxicological Research

  • 제30권4호
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  • Pages.261-266
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  • 2014
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  • 1976-8257(pISSN)
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  • 2234-2753(eISSN)
한국독성학회 (Korean Society of Toxicology & Korea Environmental Mutagen Society)
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Transformation of Mouse Liver Cells by Methylcholanthrene Leads to Phenotypic Changes Associated with Epithelial-mesenchymal Transition

  • Oh, Jiyun (College of Pharmacy, Pusan National University) ;
  • Kwak, Jae-Hwan (College of Pharmacy, Kyungsung University) ;
  • Kwon, Do-Young (Risk Assessment Division, National Institute of Environmental Research) ;
  • Kim, A-Young (College of Pharmacy, Pusan National University) ;
  • Oh, Dal-Seok (Korea Institute of Oriental Medicine) ;
  • Je, Nam Kyung (College of Pharmacy, Pusan National University) ;
  • Lee, Jaewon (College of Pharmacy, Pusan National University) ;
  • Jung, Young-Suk (College of Pharmacy, Pusan National University)
  • 투고 : 2014.12.17
  • 심사 : 2014.12.22
  • 발행 : 2014.12.31
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초록

Environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs) have been implicated in cancer development and progression. However, the effects of PAHs on carcinogenesis are still poorly understood. Here, we characterized a mouse cancer cell line BNL 1ME A. 7R.1 (1MEA) derived by transformation of non-tumorigenic liver cell line BNL CL.2 (BNL) using 3-methylcholanthrene (3MC), a carcinogenic PAH. RT-PCR and immunoblot analysis were used to determine the expression level of mRNA and proteins, respectively. To determine functionality, cell motility was assessed in vitro using a transwell migration assay. Both mRNA and protein levels of E-cadherin were significantly decreased in 1MEA cells in comparison with BNL cells. While the expression levels of mesenchymal markers and related transcription factors were enhanced in 1MEA cells, which could lead to increase in cell motility. Indeed, we found that 7-day exposure of BNL cells to 3-MC reduced the level of the adhesion molecule and epithelial marker E-cadherin and increased reciprocally the level of the mesenchymal marker vimentin in a dose-dependent manner. Taken together, these results indicate that the process of epithelial-mesenchymal transition (EMT) may be activated during premalignant transformation induced by 3-MC. A mechanism study to elucidate the relation between 3-MC exposure and EMT is underway in our laboratory.

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참고문헌

  1. Kim, K.H., Jahan, S.A., Kabir, E. and Brown, R.J. (2013) A review of airborne polycyclic aromatic hydrocarbons (PAHs) and their human health effects. Environ. Int., 60, 71-80. https://doi.org/10.1016/j.envint.2013.07.019
  2. Pelclova, D., Fenclova, Z., Dlaskova, Z., Urban, P., Lukas, E., Prochazka, B., Rappe, C., Preiss, J., Kocan, A. and Vejlupkova, J. (2001) Biochemical, neuropsychological, and neurological abnormalities following 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) exposure. Arch. Environ. Health, 56, 493-500. https://doi.org/10.1080/00039890109602897
  3. Baccarelli, A., Mocarelli, P., Patterson, D.G. Jr., Bonzini, M., Pesatori, A.C., Caporaso, N. and Landi, M.T. (2002) Immunologic effects of dioxin: new results from Seveso and comparison with other studies. Environ. Health Perspect., 110, 1169-1173. https://doi.org/10.1289/ehp.021101169
  4. Pesatori, A.C., Consonni, D., Bachetti, S., Zocchetti, C., Bonzini, M., Baccarelli, A. and Bertazzi, P.A. (2003) Shortand long-term morbidity and mortality in the population exposed to dioxin after the "Seveso accident". Ind. Health, 41, 127-138. https://doi.org/10.2486/indhealth.41.127
  5. Denison, M.S., Pandini, A., Nagy, S.R., Baldwin, E.P. and Bonati, L. (2002) Ligand binding and activation of the Ah receptor. Chem. Biol. Interact., 141, 3-24. https://doi.org/10.1016/S0009-2797(02)00063-7
  6. Denison, M.S. and Nagy, S.R. (2003) Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annu. Rev. Pharmacol. Toxicol., 43, 309-334. https://doi.org/10.1146/annurev.pharmtox.43.100901.135828
  7. Nebert, D.W., Dalton, T.P., Okey, A.B. and Gonzalez, F.J. (2004) Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer. J. Biol. Chem., 279, 23847-23850. https://doi.org/10.1074/jbc.R400004200
  8. Yang, X., Solomon, S., Fraser, L.R., Trombino, A.F., Liu, D., Sonenshein, G.E., Hestermann, E.V. and Sherr, D.H. (2008) Constitutive regulation of CYP1B1 by the aryl hydrocarbon receptor (AhR) in pre-malignant and malignant mammary tissue. J. Cell. Biochem., 104, 402-417. https://doi.org/10.1002/jcb.21630
  9. Yang, X., Liu, D., Murray, T.J., Mitchell, G.C., Hesterman, E.V., Karchner, S.I., Merson, R.R., Hahn, M.E. and Sherr, D.H. (2005) The aryl hydrocarbon receptor constitutively represses c-myc transcription in human mammary tumor cells. Oncogene, 24, 7869-7881. https://doi.org/10.1038/sj.onc.1208938
  10. Villano, C.M., Murphy, K.A., Akintobi, A. and White, L.A. (2006) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces matrix metalloproteinase (MMP) expression and invasion in A2058 melanoma cells. Toxicol. Appl. Pharmacol., 210, 212-224. https://doi.org/10.1016/j.taap.2005.05.001
  11. Abercrombie, M. (1979) Contact inhibition and malignancy. Nature, 281, 259-262. https://doi.org/10.1038/281259a0
  12. Kang, Y. and Massague, J. (2004) Epithelial-mesenchymal transitions: twist in development and metastasis. Cell, 118, 277-279. https://doi.org/10.1016/j.cell.2004.07.011
  13. Kalluri, R. and Weinberg, R.A. (2009) The basics of epithelial-mesenchymal transition. J. Clin. Invest., 119, 1420-1428. https://doi.org/10.1172/JCI39104
  14. Thiery, J.P., Acloque, H., Huang, R.Y. and Nieto, M.A. (2009) Epithelial-mesenchymal transitions in development and disease. Cell, 139, 871-890. https://doi.org/10.1016/j.cell.2009.11.007
  15. Acloque, H., Adams, M.S., Fishwick, K., Bronner-Fraser, M. and Nieto, M.A. (2009) Epithelial-mesenchymal transitions: the importance of changing cell state in development and disease. J. Clin. Invest., 119, 1438-1449. https://doi.org/10.1172/JCI38019
  16. Zeisberg, M. and Neilson, E.G. (2009) Biomarkers for epithelial-mesenchymal transitions. J. Clin. Invest., 119, 1429-1437. https://doi.org/10.1172/JCI36183
  17. Diry, M., Tomkiewicz, C., Koehle, C., Coumoul, X., Bock, K.W., Barouki, R. and Transy, C. (2006) Activation of the dioxin/aryl hydrocarbon receptor (AhR) modulates cell plasticity through a JNK-dependent mechanism. Oncogene, 25, 5570-5574. https://doi.org/10.1038/sj.onc.1209553
  18. Bui, L.C., Tomkiewicz, C., Chevallier, A., Pierre, S., Bats, A.S., Mota, S., Raingeaud, J., Pierre, J., Diry, M., Transy, C., Garlatti, M., Barouki, R. and Coumoul, X. (2009) Nedd9/Hef1/Cas-L mediates the effects of environmental pollutants on cell migration and plasticity. Oncogene, 28, 3642-3651. https://doi.org/10.1038/onc.2009.224
  19. Ikuta, T. and Kawajiri, K. (2006) Zinc finger transcription factor Slug is a novel target gene of aryl hydrocarbon receptor. Exp. Cell Res., 312, 3585-3594. https://doi.org/10.1016/j.yexcr.2006.08.002
  20. Harvey, R.G. (1982) Polycyclic hydrocarbons and cancer. Am. Sci., 70, 386-393.
  21. Guengerich, F.P. (1990) Enzymatic oxidation of xenobiotic chemicals. Crit. Rev. Biochem. Mol. Biol., 25, 97-153. https://doi.org/10.3109/10409239009090607
  22. Thiery, J.P. (2002) Epithelial-mesenchymal transitions in tumour progression. Nat. Rev. Cancer, 2, 442-454. https://doi.org/10.1038/nrc822
  23. Sanchez-Tillo, E., Liu, Y., de Barrios, O., Siles, L., Fanlo, L., Cuatrecasas, M., Darling, D.S., Dean, D.C., Castells, A. and Postigo, A. (2012) EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness. Cell. Mol. Life Sci., 69, 3429-3456. https://doi.org/10.1007/s00018-012-1122-2
  24. Puisieux, A., Brabletz, T. and Caramel, J. (2014) Oncogenic roles of EMT-inducing transcription factors. Nat. Cell Biol., 16, 488-494. https://doi.org/10.1038/ncb2976
  25. Nieto, M.A. (2013) Epithelial plasticity: a common theme in embryonic and cancer cells. Science, 342, 1234850. https://doi.org/10.1126/science.1234850
  26. Taube, J.H., Herschkowitz, J.I., Komurov, K., Zhou, A.Y., Gupta, S., Yang, J., Hartwell, K., Onder, T.T., Gupta, P.B., Evans, K.W., Hollier, B.G., Ram, P.T., Lander, E.S., Rosen, J.M., Weinberg, R.A. and Mani, S.A. (2010) Core epithelialto-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes. Proc. Natl. Acad. Sci. U.S.A., 107, 15449-15454. https://doi.org/10.1073/pnas.1004900107
  27. Reinhold, W.C., Reimers, M.A., Lorenzi, P., Ho, J., Shankavaram, U.T., Ziegler, M.S., Bussey, K.J., Nishizuka, S., Ikediobi, O., Pommier, Y.G. and Weinstein, J.N. (2010) Multifactorial regulation of E-cadherin expression: an integrative study. Mol. Cancer Ther., 9, 1-16.

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