350 rub
Journal Technologies of Living Systems №7 for 2013 г.
Article in number:
Mycoplasma increased resistance of H292 lung cancer cell line to Nutlin3 through activation of nfkb signaling pathway
Keywords: nonsmall cell lung cancer transcriptome analysis mycoplasma signaling pathways apoptosis
Authors:
U.A. Boyarskih, D.A. Zhechev, V.V. Kozlov, M.A. Smetanina, A.E. Kel, M.L. Filipenko
Abstract:
Nutlin3 is an antitumor compound that selectively induces cell cycle arrest and death of tumor cells through p53 reactivation. We examined effect of Mycoplasma hyorhinis on the sensitivity of H292 cells to Nutlin3. Mycoplasma infection reduces the cytotoxic effects of Nutlin3 on NCI-N292 cells (in cell culture infected with M. hyorhinis the percentage of viable cells after incubation with 30 µM Nutlin3 was significantly higher than in uninfected cell culture; 11,5±5,2 vs 59,5±11,4; p<0,001). Additionally, еpithelial mesenchymal transformation of cell culture was a concomitant effect of mycoplasma infection. Microarray-based transcriptome analysis of infected and uninfected cells revealed the activation of IL-1/NFkB signaling pathway in H292 cells infected with M. hyorhinis. This finding suggests that activation of IL-1/NFkB signaling pathway is the most likely mechanism of H292 cells resistance to Nutlin3.
Pages: 45-50
References

  1. Razin S., Yogev D., Naot Y. Molecular biology and pathogenicity of mycoplasmas // Microbiol. Mol. Biol. Rev. 1998. V. 62. № 4. P. 1094-1156.
  2. Kel A., Voss N., Jauregui R., Kel-Margoulis O., Wingender E. Beyond microarrays: Finding key transcription factors controlling signal transduction pathways // BMC Bioinformatics. 2006. V. 7. Suppl. 2. S. 13.
  3. Vassilev L.T., Vu B.T., Graves B. et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2 // Science. 2004. V. 303. № 5659. P. 844-848.
  4. Feng S.H., Tsai S., Rodriguez J. et al. Mycoplasmal infections prevent apoptosis and induce malignant transformation of interleukin-3-dependent 32D hematopoietic cells // Mol. Cell Biol. 1999. V. 19. № 12. P. 7995-8002.
  5. Logunov D.Y., Scheblyakov D.V., Zubkova O.V. et al. Mycoplasma infection suppresses p53, activates NF-kappaB and cooperates with oncogenic Ras in rodent fibroblast transformation // Oncogene. 2008. V. 27, № 33. P. 4521-4531.
  6. Takeda K., Takeuchi O., Akira S. Recognition of lipopeptides by Toll-like receptors // J. Endotoxin Res. 2002. V. 8. P. 459-463.
  7. Karin M. Nuclear factor-κB in cancer development and progression. // Nature. 2006. V. 441. № 25. P. 431-436.
  8. Wenbin Liu, Chengchao Shou. Mycoplasma hyorhinis and Mycoplasma fermentans induce cell apoptosis and changes in gene expression profiles of 32D cells // Biol. Res. 2011. V. 44. P. 383-391.
  9. Han Z., Zhang S., Liu Y. et al. Epithelial-Mesenchymal Transition in tumor microenvironment // Cell & Bioscience. 2011. V. 1. № 29. P. 1-7.
  10. Hofland J., van Weerden W.M., Steenbergen J. et al. Activin A stimulates AKR1C3 expression and growth in human prostate cancer // Endocrinology. 2012. V. 153. № 12. P. 5726-5734.
  11. Cieply B., Riley P., Pifer P.M. Suppression of the epithelial-mesenchymal transition by Grainyhead-like-2 // Cancer Res. 2012. V. 72. № 9. P. 2440-2453.
  12. Gaengel K., Niaudet K., Hagikura K. et al. The sphingosine-1-phosphate receptor S1PR1 restricts sprouting angiogenesis by regulating the interplay between ve-cadherin and VEGFR2 // Developmental Cell. 2012. V. 23. № 3. P 587-599.
  13. Griner S.E., Joshi J.P., Nahta R. Growth differentiation factor 15 stimulates rapamycin-sensitive ovarian cancer cell growth and invasion // Biochem. Pharmacol. 2013. V. 85. № 1. P. 46-58.
  14. Qian Y., Jung Y.S., Chen X. Differentiated embryo-chondrocyte expressed gene 1 regulates p53-dependent cell survival versus cell death through macrophage inhibitory cytokine-1 // Proc. Natl. Acad. Sci. USA. 2012. V. 109. № 28. P. 11300-11305.
  15. Jiang S., Zhang S., Langenfeld J. et al. Mycoplasma infection transforms normal lung cells and induces bone morphogenetic protein 2 expression by post-transcriptional mechanisms // J. Cell. Biochemistry. 2008. V. 104. P. 580-594.