Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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In Silico Interaction and Docking Studies Indicate a New Mechanism for PML Dysfunction in Gastric Cancer and Suggest Imatinib as a Drug to Restore Function

  • Imani-Saber, Zeinab (Department of Medical Genetics, Shahid Beheshti University of Medical Sciences) ;
  • Ghafouri-Fard, Soudeh (Department of Medical Genetics, Shahid Beheshti University of Medical Sciences)
  • Published : 2015.07.13
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Abstract

Gastric cancer as one of the most common cancers worldwide has various genetic and environmental risk factors including Helicobacter pylori (H.pylori) infection. Recently, loss of a tumor suppressor gene named promyelocytic leukemia (PML) has been identified in gastric cancer. However, no mutation has been found in this gene in gastric cancer samples. Cag A H.pylori protein has been shown to exert post transcriptional regulation of some tumor suppressor genes. In order to assess such a mechanism for PML degradation, we performed in silico analyses to establish any interaction between PML and Cag A proteins. In silico interaction and docking studies showed that these two proteins may have stable interactions. In addition, we showed that imatinib kinase inhibitor can restore PML function by inhibition of casein kinase 2.

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References

  1. Fock KM (2014). Review article: the epidemiology and prevention of gastric cancer. Aliment Pharmacol Ther, 40, 250-60. https://doi.org/10.1111/apt.12814
  2. Imani-Saber Z, Ghafouri-Fard S (2014). Promyelocytic leukemia gene functions and roles in tumorigenesis. Asian Pac J Cancer Prev, 15, 8021-8.
  3. Imani-Saber Z, Yousefi-Razin E, Javaheri M, et al (2015). PML gene mutations do not contribute in gastric adenocarcinoma. Asian Pac J Cancer Prev, [Epub ahead of print].
  4. Kim HJ, Song DE, Lim SY, et al (2011). Loss of the promyelocytic leukemia protein in gastric cancer: implications for IP-10 expression and tumor-infiltrating lymphocytes. PLoS One, 6, 26264. https://doi.org/10.1371/journal.pone.0026264
  5. Lee HE, Jee CD, Kim MA, et al (2007). Loss of promyelocytic leukemia protein in human gastric cancers. Cancer Lett, 247, 103-9. https://doi.org/10.1016/j.canlet.2006.03.034
  6. Sivachandran N, Cao JY, Frappier L (2010). Epstein-Barr virus nuclear antigen 1 Hijacks the host kinase CK2 to disrupt PML nuclear bodies. J Virol, 84, 11113-23. https://doi.org/10.1128/JVI.01183-10
  7. Sivachandran N, Dawson CW, Young LS, et al (2012). Contributions of the Epstein-Barr virus EBNA1 protein to gastric carcinoma. J Virol, 86, 60-8. https://doi.org/10.1128/JVI.05623-11
  8. Wei J, Nagy TA, Vilgelm A, et al (2010). Regulation of p53 tumor suppressor by Helicobacter pylori in gastric epithelial cells. Gastroenterol, 139, 1333-43. https://doi.org/10.1053/j.gastro.2010.06.018