Parkin-induced Decrease of ${\beta}$-catenin is Mediated by Protein Kinase C in TNF-${\alpha}$-treated HeLa Cells

  • Lee, Min Ho (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Jung, Byung Chul (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Kim, Sung Hoon (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Lee, Juyeon (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Jung, Dongju (Department of Physiology, University of Oklahoma Health Sciences Center) ;
  • Cho, Jang-Eun (Department of Biomedical Laboratory Science, Daegu Health College) ;
  • Rhee, Ki-Jong (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University) ;
  • Kim, Yoon Suk (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University)
  • 투고 : 2013.06.14
  • 심사 : 2013.06.17
  • 발행 : 2013.06.29

초록

Parkin is a protein known to have tumor suppressive functions. In a previous study, we determined that Parkin expression restores susceptibility to TNF-${\alpha}$-induced death in HeLa cells. ${\beta}$-catenin is a key protein in the Wnt signaling pathway and excessive activation of the ${\beta}$-catenin pathway can promote cancer development. In this study, we found that ${\beta}$-catenin levels decreased dramatically in Parkin over-expressing HeLa cells treated with TNF-${\alpha}$. We used chemical inhibitors of cell signaling pathways to identify the signaling molecules involved in ${\beta}$-catenin down-regulation. Our results indicate that the PKC inhibitor (RO-31-7549) blocked parkin-induced down-regulation of ${\beta}$-catenin. We also show that Parkin-induced decrease in cell viability in TNF-${\alpha}$-treated HeLa cells is alleviated upon treatment with a PKC inhibitor. Taken together, these results suggest the possibility that ${\beta}$-catenin reduction may be associated with Parkin-induced decrease of cell viability in TNF-${\alpha}$ treated HeLa cells.

키워드

참고문헌

  1. Agirre X, Roman-Gomez J, Vazquez I, Jimenez-Velasco A, Garate L, Montiel-Duarte C, Artieda P, Cordeu L, Lahortiga I, Calasanz MJ, Heiniger A, Torres A, Minna JD, Prosper F. Abnormal methylation of the common PARK2 and PACRG promoter is associated with downregulation of gene expression in acute lymphoblastic leukemia and chronic myeloid leukemia. Int J Cancer. 2006. 118: 1945-1953. https://doi.org/10.1002/ijc.21584
  2. Altieri DC. Molecular circuits of apoptosis regulation and cell division control: the survivin paradigm. J Cell Biochem. 2004. 92: 656-663. https://doi.org/10.1002/jcb.20140
  3. Balkwill F. Tumour necrosis factor and cancer. Nat Rev Cancer. 2009. 9: 361-371. https://doi.org/10.1038/nrc2628
  4. Beachy PA, Karhadkar SS, Berman DM. Tissue repair and stem cell renewal in carcinogenesis. Nature. 2004. 432: 324-331. https://doi.org/10.1038/nature03100
  5. Capaldo CT, Beeman N, Hilgarth RS, Nava P, Louis NA, Naschberger E, Sturzl M, Parkos CA, Nusrat A. IFN-${\gamma}$ and TNF-${\alpha}$-induced GBP-1 inhibits epithelial cell proliferation through suppression of ${\beta}$-catenin/TCF signaling. Mucosal Immunol. 2012. 5: 681-690. https://doi.org/10.1038/mi.2012.41
  6. Chen S, Guttridge DC, You Z, Zhang Z, Fribley A, Mayo MW, Kitajewski J, Wang CY. Wnt-1 signaling inhibits apoptosis by activating ${\beta}$-catenin/T cell factor-mediated transcription. J Cell Biol. 2001. 152: 87-96. https://doi.org/10.1083/jcb.152.1.87
  7. Denison SR, Callahan G, Becker NA, Phillips LA,Smith DI. Characterization of FRA6E and its potential role in autosomal recessive juvenile parkinsonism and ovarian cancer. Genes Chromosomes Cancer. 2003a. 38: 40-52. https://doi.org/10.1002/gcc.10236
  8. Denison SR, Wang F, Becker NA, Schule B, Kock N, Phillips LA, Klein C, Smith DI. Alterations in thecommon fragile site gene Parkin in ovarian and other cancers. Oncogene. 2003b. 22: 8370-8378. https://doi.org/10.1038/sj.onc.1207072
  9. Franco DL, Nojek IM, Molinero L, Coso OA, Costas MA. Osmotic stress sensitizes naturally resistant cells to TNF-${\alpha}$ -induced apoptosis. Cell Death Differ. 2002. 9: 1090-1098. https://doi.org/10.1038/sj.cdd.4401074
  10. Heeg-Truesdell E, LaBonne C. Wnt signaling: a shaggy dogma tale. Curr Biol. 2006. 16: R62-64. https://doi.org/10.1016/j.cub.2006.01.004
  11. Kim YS, Patel S, Lee SJ. Lack of direct role of parkin in the steady-state level and aggregation of ${\alpha}$-synuclein and the clearance of pre-formed aggregates. Exp Neurol. 2006. 197: 538-541. https://doi.org/10.1016/j.expneurol.2005.10.024
  12. Kimelman D, Xu W. ${\beta}$-catenin destruction complex: insights and questions from a structural perspective. Oncogene. 2006. 25: 7482-7491. https://doi.org/10.1038/sj.onc.1210055
  13. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998. 392: 605-608. https://doi.org/10.1038/33416
  14. Kong FM, Anscher MS, Washington MK, Killian JK, Jirtle RL. M6P/IGF2R is mutated in squamous cell carcinoma of the lung. Oncogene. 2000. 19: 1572-1578. https://doi.org/10.1038/sj.onc.1203437
  15. Lee KH, Lee MH, Kang YW, Rhee K-J, Kim TU, Kim YS. Parkin induces apoptotic cell death in TNF-${\alpha}$-treated cervical cancer cells. BMB Rep. 2012. 45: 526-531. https://doi.org/10.5483/BMBRep.2012.45.9.104
  16. Nagy JA, Dvorak AM, Dvorak HF. VEGF-A and the induction of pathological angiogenesis. Annu Rev Pathol. 2007. 2: 251-275. https://doi.org/10.1146/annurev.pathol.2.010506.134925
  17. Oates AJ, Schumaker LM, Jenkins SB, Pearce AA, DaCosta SA, Arun B, Ellis MJ. The mannose 6-phosphate /insulin-like growth factor 2 receptor (M6P/IGF2R), a putative breast tumor suppressor gene. Breast Cancer Res Treat. 1998. 47: 269-281. https://doi.org/10.1023/A:1005959218524
  18. Picchio MC, Martin ES, Cesari R, Calin GA, Yendamuri S, Kuroki T, Pentimalli F, Sarti M, Yoder K, Kaiser LR, Fishel R, Croce CM. Alterations of the tumor suppressor gene Parkin in non-small cell lung cancer. Clin Cancer Res. 2004. 10: 2720-2724. https://doi.org/10.1158/1078-0432.CCR-03-0086
  19. Poulogiannis G, McIntyre RE, Dimitriadi M, Apps JR, Wilson CH, Ichimura K, Luo F, Cantley LC, Wyllie AH, Adams DJ, Arends MJ. PARK2 deletions occur frequently in sporadic colorectal cancer and accelerate adenoma development in Apc mutant mice. Proc Natl Acad Sci U S A. 2010. 107: 15145-15150. https://doi.org/10.1073/pnas.1009941107
  20. Shang XZ, Zhu H, Lin K, Tu Z, Chen J, Nelson DR, Liu C. Stabilized ${\beta}$-catenin promotes hepatocyte proliferation and inhibits TNF ${\alpha}$-induced apoptosis. Lab Invest. 2004. 84: 332-341. https://doi.org/10.1038/labinvest.3700043
  21. Shridhar V, Staub J, Huntley B, Cliby W, Jenkins R, Pass HI, Hartmann L, Smith DI. A novel region of deletion on chromosome 6q23.3 spanning less than 500 Kb in high grade invasive epithelial ovarian cancer. Oncogene. 1999. 18: 3913-3918. https://doi.org/10.1038/sj.onc.1202756
  22. Tay SP, Yeo CW, Chai C, Chua PJ, Tan HM, Ang AX, Yip DL, Sung JX, Tan PH, Bay BH, Wong SH, Tang C, Tan JM, Lim KL. Parkin enhances the expression of cyclin-dependent kinase 6 and negatively regulates the proliferation of breast cancer cells. J Biol Chem. 2010. 285: 29231-29238. https://doi.org/10.1074/jbc.M110.108241
  23. Veeriah S, Taylor BS, Meng S, Fang F, Yilmaz E, Vivanco I, Janakiraman M, Schultz N, Hanrahan AJ, Pao W, Ladanyi M, Sander C, Heguy A, Holland EC, Paty PB, Mischel PS, Liau L, Cloughesy TF, Mellinghoff IK, Solit DB, Chan TA. Somatic mutations of the Parkinson's disease-associated gene PARK2 in glioblastoma and other human malignancies. Nat Genet. 2010. 42: 77-82. https://doi.org/10.1038/ng.491
  24. Wang F, Denison S, Lai JP, Philips LA, Montoya D, Kock N, Schule B, Klein C, Shridhar V, Roberts LR, Smith DI. Parkin gene alterations in hepatocellular carcinoma. Genes Chromosomes Cancer. 2004. 40: 85-96. https://doi.org/10.1002/gcc.20020