Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Sodium Butyrate Alters Cell-Cell Interactions through Up-Regulation of E-Cadherin in Human Hepatocellular Carcinoma Cells

Sodium butyrate에 의한 E-cadherin의 발현증가와 세포간 상호작용의 변화

  • Kwun, Hyun-Jin (Department of Microbiology, College of Natural Sciences, Pusan National University) ;
  • Jang, Kyung-Lib (Department of Microbiology, College of Natural Sciences, Pusan National University)
  • 권현진 (부산대학교 자연과학대학 미생물학과) ;
  • 장경립 (부산대학교 자연과학대학 미생물학과)
  • Published : 2009.06.30
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Abstract

Sodium butyrate (NaBt), a naturally occurring short chain fatty acid derived from carbohydrate metabolism in the gut, is known to exhibit strong anti-cancer potentials in various human cancer cells; however, its action mechanism is poorly understood. In the present study, we demonstrated that NaBt up-regulates levels of E-cadherin, a key cell adhesion molecule implicated as a tumor suppressor, in a cell type-specific manner. Although levels of p21, a potential activator for E-cadherin expression, were also up-regulated by treatment with NaBt in several types of cells, it does not seem to be associated with the activation of E-cadherin in the NaBt-treated cells. Instead, the data from promoter analysis suggest that NaBt up-regulates expression of E-cadherin at the transcription level by enhancing its promoter strength via a CCAAT-box. The elevated E-cadherin in the presence of NaBt was primarily localized at the cell-cell contacts, converting Hep3B cells into a more differentiated form.

Sodium butyrate (NaBt)는 장에서 탄수화물대사로부터 생겨나는 짧은 천연지방산 사슬로 다양한 인간 암세포들 에게서 강력한 항암효능을 나타냄이 보고된 바 있지만 자세한 기전은 아직 알려져 있지 않다. 이 논문에서 우리는 NaBt가 주요 세포부착분자이면서 종양억제인자의 일종인 E-cadherin의 발현을 세포-특이적으로 촉진하는 기전을 연구하였다. 또한 NaBt는 E-eadherin의 발현을 촉진하는 것으로 알려진 p21의 발현도 증가시켰지만, NaBt에 의하여 증가한 p21은 E-cadherin의 활성화와 관련이 없음이 밝혀졌다. 그 대신에 NaBt는 CCAAT-box를 통한 E-cadherin 유전자의 프로모터 활성을 증가시킴으로써 E-cadherin의 발현을 전사수준에서 촉진하는 것 같다. 이렇게 NaBt에 의하여 증가된 E-cadherin은 주로 세포간 접촉면에 위치하면서 Hep3B 세포를 더 분화된 형태로 유도하여 NaBt의 항암활성이 나타나는 것 같다.

Keywords

References

  1. Batlle, E., E. Sancho, C. Franci, D. Dominguez, M. Monfar, J. Baulida, and A. Garcia De Herreros. 2000. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat. Cell Biol. 2, 84-89 https://doi.org/10.1038/35000034
  2. Batsche, E., C. Muchardt, J. Behrens, H. C. Hurst, and C. Cremisi. 1998. RB and c-Myc activate expression of the E-cadherin gene in epithelial cells through interaction with transcription factor AP-2. Mol. Cell Biol. 18, 3647-3658
  3. Bukholm, I. K., J. M. Nesland, R. Karesen, U. Jacobsen, and A. L. Borresen-Dale. 1997. Expression of E-cadherin and its relation to the p53 protein status in human breast carcinomas. Virchows Arch. 431, 317-321 https://doi.org/10.1007/s004280050105
  4. Bussemakers, M. J., L. A. Giroldi, A. van Bokhoven, and J. A. Schalken. 1994. Transcriptional regulation of the human E-cadherin gene in human prostate cancer cell lines: characterization of the human E-cadherin gene promoter. Biochem. Biophys. Res. Commun. 203, 1284-1290 https://doi.org/10.1006/bbrc.1994.2321
  5. Chaudhry, A. Z., A. D. Vitullo, and R. M. Gronostajski. 1999. Nuclear factor I-mediated repression of the mouse mammary tumor virus promoter is abrogated by the coactivators p300/CBP and SRC-1. J. Biol. Chem. 274, 7072-7081 https://doi.org/10.1074/jbc.274.11.7072
  6. Coke, D. W. and M. D. Lane. 1988. A sequence element in the GLUT4 gene that mediates repression by insulin. J. Biol. Chem. 273, 6210-6217 https://doi.org/10.1074/jbc.273.11.6210
  7. Cooke, D. W. and M. D. Lane. 1999. The transcription factor nuclear factor I mediates repression of the GLUT4 promoter by insulin. J. Biol. Chem. 274, 12917-12924 https://doi.org/10.1074/jbc.274.18.12917
  8. Cooke, D. W. and M. D. Lane. 1999. Transcription factor NF1 mediates repression of the GLUT4 promoter by cyclic-AMP. Biochem. Biophys. Res. Commun. 260, 600-604 https://doi.org/10.1006/bbrc.1999.0959
  9. Couchie, D., N. Holic, M. N. Chobert, A. Corlu, and Y. Laperche. 2002. In vitro differentiation of WB-F344 rat liver epithelial cells into the biliary lineage. Differentiation 69, 209-215 https://doi.org/10.1046/j.1432-0436.2002.690414.x
  10. Eastman, A. 1990. Activation of programmed cell death by anticancer agents: cisplatin as a model system. Cancer Cells 2, 275-280 https://doi.org/10.1016/S1535-6108(02)00161-7
  11. Giroldi, L. A., P. P. Bringuier, M. de Weijert, C. Jansen, A. van Bokhoven, and J. A. Schalken. 1997. Role of E boxes in the repression of E-cadherin expression. Biochem Biophys. Res. Commun. 241, 453-458 https://doi.org/10.1006/bbrc.1997.7831
  12. Graff, J. R., J. G. Herman, R. G. Lapidus, H. Chopra, R. Xu, D. F. Jarrard, W. B. Isaacs, P. M. Pitha, N. E. Davidson, and S. B. Baylin. 1995. E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res. 55, 5195-5199
  13. Jackson, S. P. and R. Tjian. 1988. O-glycosylation of eukaryotic transcription factors: implications for mechanisms of transcriptional regulation. Cell 55, 125-133 https://doi.org/10.1016/0092-8674(88)90015-3
  14. Jean, D., J. E. Gershenwald, S. Huang, M. Luca, M. J. Hudson, M. A. Tainsky, and M. Bar-Eli. 1998. Loss of AP-2 results in up-regulation of MCAM/MUC18 and an increase in tumor growth and metastasis of human melanoma cells. J. Biol. Chem. 273, 16501-16508 https://doi.org/10.1074/jbc.273.26.16501
  15. Jeanes, A. and C. J. Gottardi, and A. S. Yap. 2008. Cadherins and cancer: how does cadherin dysfunction promote tumor progression? Oncogene 27, 6920-6929 https://doi.org/10.1038/onc.2008.343
  16. Kulkarni, S. and R. M. Gronostajski. 1996. Altered expression of the developmentally regulated NFI gene family during phorbol ester-induced differentiation of human leukemic cells. Cell Growth Differ. 7, 501-510
  17. Kwun, H. J., S. W. Yim, D. H. Lee, and K. L. Jang. 1997. Activation of the thymidine kinase promoter by herpes simplex virus type 1 immediate early proteins. Mol. Cells 9, 277-280
  18. Lee, W. J., H. J. Kwun, H. S. Kim, and K. L. Jang. 2003. Activation of the human endogenous retrovirus W long terminal repeat by herpes simplex virus type 1 immediate early protein 1. Mol. Cells 15, 75-80
  19. Li, L. C., R. M. Chui, M. Sasaki, K. Nakajima, G. Perinchery, H. C. Au, D. Nojima, P. Carroll, and R. Dahiya. 2000. A single nucleotide polymorphism in the E-cadherin gene promoter alters transcriptional activities. Cancer Res. 60, 873-876
  20. Momparler, R. L. and V. Bovenzi. 2000. DNA methylation and cancer. J. Cell Physiol. 183, 145-154 https://doi.org/10.1002/(SICI)1097-4652(200005)183:2<145::AID-JCP1>3.0.CO;2-V
  21. Mueller, S., E. Cadenas, and A. H. Schönthal. 2000. p21WAF1 regulates anchorage-independent growth of HCT116 colon carcinoma cells via E-cadherin expression. Cancer Res. 60, 156-163
  22. Nakano, K., T. Mizuno, Y. Sowa, T. Orita, T. Yoshino, Y. Okuyama, T. Fujita, N. Ohtani-Fujita, Y. Matsukawa, T. Tokino, H. Yamagishi, T. Oka, H. Nomura, and T. Sakai. 1997. Butyrate activates the WAF1/Cip1 gene promoter through Sp1 sites in a p53-negative human colon cancer cell line. J. Biol. Chem. 272, 22199-22206 https://doi.org/10.1074/jbc.272.35.22199
  23. Perl, A. K., P. Wilgenbus, U. Dahl, H. Semb, and G. Christofori. 1998. A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature 392, 190-193 https://doi.org/10.1038/32433
  24. Poser, I., D. Dominguez, A. G. de Herreros, A. Varnai, R. Buettner, and A. K. Bosserhoff. 2001. Loss of E-cadherin expression in melanoma cells involves up-regulation of the transcriptional repressor Snail. J. Biol. Chem. 276, 24661-24666 https://doi.org/10.1074/jbc.M011224200
  25. Sadot, E., B. Geiger, M. Oren, and A. Ben-Ze'ev. Down-regulation of beta-catenin by activated p53. Mol. Cell Biol. 21, 6768-6781
  26. Saito, H., H. Ebinuma, M. Takahashi, F. Kaneko, K. Wakabayashi, M. Nakamura, and H. Ishii. 1998. Loss of butyrate-induced apoptosis in human hepatoma cell lines HCC-M and HCC-T having substantial Bcl-2 expression. Hepatology 27, 1233-1240 https://doi.org/10.1002/hep.510270508
  27. Sun, P., P. Dong, K. Dai, G. J. Hannon, and D. Beach. 1998. p53-independent role of MDM2 in TGF-beta1 resistance. Science 282, 2270-2272 https://doi.org/10.1126/science.282.5397.2270
  28. van Roy, F. and G. Berx. 2008. The cell-cell adhesion molecule E-cadherin. Cell Mol. Life Sci. 65, 3756-3788 https://doi.org/10.1007/s00018-008-8281-1
  29. Yoshiura, K., Y. Kanai, A. Ochiai, Y. Shimoyama, T. Sugimura, and S. Hirohashi. 1995. Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc. Natl. Acad. Sci. USA 92, 7416-7419 https://doi.org/10.1073/pnas.92.16.7416