Differential gene expression by chrysotile in human bronchial epithelial cells

  • Seo, Yoo-Na (Department of Medical Biotechnology, SoonChunHyang University) ;
  • Lee, Yong-Jin (Department of Medicine, SoonChunHyung University, SoonChunHyung Environmental Health Center for Asbestos Related Disease) ;
  • Lee, Mi-Young (Department of Medical Biotechnology, SoonChunHyang University)
  • Received : 2011.04.11
  • Accepted : 2011.09.27
  • Published : 2012.04.30


Asbestos exposure has been known to contribute to several lung diseases named asbestosis, malignant mesothelioma and lung cancer, but the disease-related molecular and cellular mechanisms are still largely unknown. To examine the effects of asbestos exposure in human bronchial epithelial cells at gene level, the global gene expression profile was analyzed following chrysotile treatment. The microarray results revealed differential gene expression in response to chrysotile treatment. The genes up- and down-regulated by chrysotile were mainly involved in processes including metabolism, signal transduction, transport, development, transcription, immune response, and other functions. The differential gene expression profiles could provide clues that might be used to understand the pathological mechanisms and therapeutic targets involved in chrysotile-related diseases.



Supported by : Ministry of Environment


  1. Al-Wadei HM, Schuller HM. 2006. Cyclic AMP-dependent cell type-specific modulation of mitogenic signaling by retinoids in normal and neoplastic lung cells. Cancer Detect Prev 30:403-411.
  2. Belitskaya-Levy I, Hajjou M, Su WC, Yie TA, Tchou-Wong KM, Tang MS, Goldberg JD, Rom WN. 2007. Gene profiling of normal human bronchial epithelial cells in response to asbestos and benzo(a)pyrene diol epoxide (BPDE). J Environ Pathol Toxicol Oncol 26:281-294.
  3. Chen L, Hu J, Yun Y, Wang T. 2010. Rab36 regulates the spatial distribution of late endosomes and lysosome through a similar mechanism to Rab34. Mol Membr Biol 27:24-31.
  4. Dopp E, Yadav S, Ansari FA, Bhattacharya K, von Recklinghausen U, Rauen U, Rodelsperger K, Shokouhi B, Geh S, Rahman Q. 2005. ROS-mediated genotoxicity of asbestos-cement in mammalian lung cells in vitro. Part Fibre Toxicol 2:9.
  5. El-Said WA, Yea CH, Kim H, Oh BK, Choi JW. 2009. Cellbased chip for the detection of anticancer effect on HeLa cells using cyclic voltammetry. Biosens Bioelectron 24:1259-1265.
  6. Faux SP, Houghton CE, Hubbard A, Patrick G. 2000. Increased expression of epidermal growth factor receptor in rat pleural mesothelial cells correlates with carcinogenicity of mineral fibres. Carcinogenesis 21:2275-2280.
  7. Frank AL. 1993. Global problems from exposure to asbestos. Environ Health Perspect 3:165-167.
  8. Fung H, Kow YW, Van Houten B, Mossman BT. 1997. Patterns of 8-hydroxydeoxyguanosine formation in DNA and indications of oxidative stress in rat and human pleural mesothelial cells after exposure to crocidolite asbestos. Carcinogenesis 18:825-832.
  9. Fusello AM, Mandik-Nayak L, Shih F, Lewis RE, Allen PM, Shaw AS. 2006. The MAPK scaffold kinase suppressor of Ras is involved in ERK activation by stress and proinflammatory cytokines and induction of arthritis. J Immunol 177:6152-6158.
  10. Ghiselli G, Liu CG. 2005. Global gene expression profiling of cells overexpressing SMC3. Mol Cancer 4:1-34.
  11. Henriques SN, Vasconcellos FM, Pimenta G, Pulcheri WA, Spector N, Da Costa Carvalho Mda G. 2003. HLM/OSBP2 is expressed in chronic myeloid leukemia. Int J Mol Med 12:663-666.
  12. Kakooei H, Sameti M, Kakooei AA. 2007. Asbestos exposure during routine brake lining manufacture. Ind Health 45:787-792.
  13. Kim SJ, Park HW, Youn JP, HA JM, An YR, Lee CH, Oh MJ, Oh JH, Yoon SJ, Hwang SY. 2009. Genomic alteration of bisphenol A treatment in the testis of mice. Mol Cell Toxicol. 5:216-221.
  14. Kortenjann M, Shaw PE. 1995. The growing family of MAP kinases: regulation and specificity. Crit Rev Oncog 6:99-115.
  15. Lehto M, Olkkonen VM. 2003. The OSBP-related protein: a novel protein family involved in vesicle transport, cellular lipid metabolism, and cell signaling. Biochim Biophys Acta 1631:1-11.
  16. Levchenko A, Bruck J, Sternberg PW. 2000. Scaffold proteins may biophasically affect the levels of mitogen-activated protein kinase signaling and reduce its threshold properties. Proc Natl Acad Sci USA 97:5818-5823.
  17. Li YL, Cheng XD, Hu Y, Zhou CY, Lu WG, Xie X. 2010. Identification of glia maturation factor beta as an independent prognostic predictor for serous ovarian cancer. Eur J Cancer 46:2104-2118.
  18. Loomis D, Dement J, Richardson D, Wolf S. 2010. Asbestos fibre dimensions and lung cancer mortality among workers exposed to chrysotile. Occup Environ Med 67:580-584.
  19. Malakhova OA, Yan M, Malakhov MP, Yuan Y, Ritchie KJ, Kim KI, Peterson LF, Shuai K, Zhang DE. 2003. Protein ISGylation modulates the JAK-STAT signaling pathway. Genes Dev 17:455-460.
  20. Ng DC, Bogoyevitch MA. 2000. The mechanism of heat shock activation of ERK mitogen-activated protein kinases in the interleukin 3-dependent ProB cell line BaF3. J Biol Chem 275:40856-40866.
  21. Nymark P, Wikman H, Ruosaari S, Hollmen J, Vanhala E, Karjalainen A, Anttila S, Knuutila S. 2006. Identification of specific gene copy number changes in asbestos-related lung cancer. Cancer Res 66:5737-5743.
  22. Nymark P, Lindholm PM, Korpela MV, Lahti L, Ruosaari S, Kaski S, Hollmen J, Anttila S, Kinnula VL, Knuutila S. 2007. Gene expression profiles in asbestos-exposed epithelial and mesothelial lung cell lines. BMC Genomics 8:62.
  23. Park EK, Hannaford-Turner KM, Hyland RA, Johnson AR, Yates DH. 2008. Asbestos-related occupational lung diseases in NSW, Australia and potential exposure of the general population. Ind Health 46:535-540.
  24. Rimbault M, Robin S, Vaysse A, Galibert F. 2009. RNA profiles of rat olfactory epithelia: individual and age related variations. BMC Genomics 10:572.
  25. Riml S, Schmidt S, Ausserlechner MJ, Geley S, Kofler R. 2004. Glucocorticoid receptor heterozygosity combined with lack of receptor auto-induction causes glucocorticoid resistance in Jurkat acute lymphoblastic leukemia cells. Cell Death Differ Suppl 1:S65-S72.
  26. Robin S, Tacher S, Rimbault M, Vaysse A, Dreano S, Andre C, Hitte C, Galibert F. 2009. Genetic diversity of canine olfactory receptors. BMC Genomics 10:21.
  27. Rossana B, Carlo C, Paola M, Giovanna Z. 2009. Rocks with asbestos: risk evaluation by means of an abrasion test. Am J Environ Sci 5:500-506.
  28. Shapiro P. 2002. Ras-MAP kinase signaling pathways and control of cell proliferation: relevance to cancer therapy. Crit Rev Clin Lab Sci 39:285-330.
  29. Shaul YD, Seger R. 2007. The MEK/ERK cascade: from signaling specificity to diverse functions. Biochim Biophys Acta 1773:1213-1226.
  30. Shukla A, Ramos-Nino M, Mossman B. 2003. Cell signaling and transcription factor activation by asbestos in lung injury and disease. Int J Biochem Cell Biol 35:1198-1209.
  31. Xu A, Wu LJ, Santella RM, Hei TK. 1999. Role of oxyradicals in mutagenicity and DNA damage induced by crocidolite asbestos in mammalian cells. Cancer Res 59:5922-5926.