Journal of Food Hygiene and Safety (한국식품위생안전성학회지)

The Korean Society of Food Hygiene and Safety (한국식품위생안전성학회)
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Tumor Necrosis Factor-Alpha $(TNF-{\alpha})$ Induces PTEN Expression in HL-60 Cells

백혈병세포에서 종양괴사인자에 의한 PTEN 발현증가

  • Lee Seung-Ho (Department of Nursing, College of Visual image & Health, Kongju National University) ;
  • Park Chul-Hong (Department of Biochemistry, Medical School and Institute of Medical Science, Chonbuk National University) ;
  • Kim Byeong-Su (Department of Companion and Laboratory Animal Science, College of Industrial Science, Kongju National University)
  • 이성호 (공주대학교 영상보건대학 간호학과) ;
  • 박철홍 (전북대학교 의과대학 생화학교실 의과학연구소) ;
  • 김병수 (공주대학교 산업과학대학 특수동물학과)
  • Published : 2006.09.01
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Abstract

Tumor necrosis factor-alpha $(TNF-{\alpha})$ plays a variety of biological functions such as apoptosis, inflammation and immunity. PTEN also has various cellular function including cell growth, proliferation, migration and differentiation. Thus, possible relationships between two molecules are suggested. $(TNF-{\alpha})$has been known to downregulate PTEN via nuclear factor-kappa $B(NF-{\kappa}B)$ pathway in the human colon cell line, HT-29. However, here we show the opposite finding that $(TNF-{\alpha})$ upregulates PTEN via activation of $NF-{\kappa}B$ in HL-60 cells. $TNF-{\alpha}$ increased PTEN expression at HL-60 cells in a time- and dose-dependent manner, but the response was abolished by disruption of $NF-{\kappa}B$ with p65 anisense oligonucleotide or pyrrolidine dithiocarbamate (PDTC). We found that $TNF-{\alpha}$ activated the $NF-{\kappa}B$ pathways, evidenced by the translocation of p65 to the nucleus in $TNF-{\alpha}-treated$ cells. We conclude that $TNF-{\alpha}$ induces upregulation of PTEN expression through $NF-{\kappa}B$ activation in HL-60 cells.

Tumor necrosis ftctor-alpha$(TNF-{\alpha})$는 세포의 고사, 염증 및 면역 등의 다양한 생물학적 기능에 대한 역할을 한다. PTEN 역시 세포의 성장과 증식 그리고 세포의 유주와 분화 등의 세포학적인 다양한 기능을 갖는다 그러므로 이들 두 분자들 사이의 상호관계가 있을 것으로 제안되고 있으며, $TNF-{\alpha}$는 사람의 대장세포 주인 HT-29에서 nuclear factor-kappa $B(NF-{\kappa}B)$ 경로를 통해 PTEN downregulate 기능이 있는 것으로 알려져 왔다. 그러나 저자 등은 본 연구에서 HL-60 cells에서 $TNF-{\alpha}$가 $NF-{\kappa}B$를 통해 PTEN를 upregulates하는 기존의 반대 현상을 확인하였다. $TNF-{\alpha}$는 HL-60 cells에서 time과 dose의존성 방법으로 PTEN 발현을 증가시켰지만 반응은 p65 anisense oligonucleotide 또는 pyrrolidine dithiocarbamate(PDTC)으로 $NF-{\kappa}B$를 분해함으로 파괴되었다. 따라서 저자 등은 $TNF-{\alpha}$가 $NF-{\kappa}B$경로를 활성화시킴을 확인하였고, $TNF-{\alpha}$를 처리 할 경우 핵에 대하여 p65 전위에 의해 $TNF-{\alpha}$가 활성화됨을 증명하였다. 결국 HL-60세포에서 $NF-{\kappa}B$의 활성화에 따라 PTEN 발현의 upregulation이 유도되는 것으로 결론지었다.

Keywords

References

  1. Vivanco, I. and Sawyers, C.L. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat. Rev. Cancer 2, 489-501 (2002) https://doi.org/10.1038/nrc839
  2. Maehama, T., and Dixon, J.E. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5,-triphosphate. J. Biol. Chem. 273, 13375-13378 (1998) https://doi.org/10.1074/jbc.273.22.13375
  3. Myers, M.P., Pass, I., Batty, I.H., Van der Kaay, J., Stolarov, J.P., Hemmings, B.A., Wigler, M.H., Downes, C.P., and Tonks, N.K. The lipid phosphatase activity of PTEN is critical for its tumor suppressor function. Proc. Natl. Acad. Sci. U.S.A. 95, 13513-13518 (1998)
  4. Tonks, N.K. and Myers, M.P. Structural assets of a tumor suppressor. Science 286, 2096-2097 (1999) https://doi.org/10.1126/science.286.5447.2096
  5. Samuels, Y. and Ericson, K. Oncogenic PI3K and its role in cancer. Curr. Opin. Oncol. 1, 77-82 (2006)
  6. Hennessy, B.T., Smith, D.L., Ram, P.T., Lu, Y., and Mills, G.B. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat. Rev. Drug Discov. 4, 988-1004 (2005) https://doi.org/10.1038/nrd1902
  7. Morgensztern, D. and McLeod, H.L. PI3K/Akt/mTOR pathway as a target for cancer therapy. Anticancer Drugs 16, 797-803 (2005) https://doi.org/10.1097/01.cad.0000173476.67239.3b
  8. Lachyankar, M.B., Sultana, N., Schonhoff, C.M., Mitra, P., Poluha, W., Lambert, S., Quesenberry, P.J., Litofsky, N.S., Recht, L.D., Nabi, R., Miller, S.J., Ohta, S., Neel, B.G., and Ross, A.H. A role for nuclear PTEN in neuronal differentiation. J. Neurosci. 20, 1404-1413 (2004)
  9. Kurose, K., Zhou, X.P., Araki, T., Cannistra, S.A., Maher, E.R., and Eng, C. Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels, but not associated with p27 and cyclin D1 expression, in primary epithelial ovarian carcinomas. Am. J. Pathol. 158, 2097-106 (2001) https://doi.org/10.1016/S0002-9440(10)64681-0
  10. Stambolic, V., MacPherson, D, Sas, D., Lin, Y., Snow, B., Jang, Y., Benchimol, S., and Mak, T.W. Regulation of PTEN transcription by p53. Mol. Cell 8, 317-325 (2001) https://doi.org/10.1016/S1097-2765(01)00323-9
  11. Sheng, X, Koul, D, Liu, JL, Liu, TJ, and Yung, W.K. Promoter analysis of tumor suppressor gene PTEN: identification of minimum promoter region. Biochem. Biophys. Res. Commun. 292, 422-426 (2002) https://doi.org/10.1006/bbrc.2002.6662
  12. Tang, Y, and Eng, C. PTEN autoregulates its expression by stabilization of p53 in a phosphatase-independent manner. Cancer Res. 66, 736-742 (2006) https://doi.org/10.1158/0008-5472.CAN-05-1557
  13. Kim, S., Domon-Dell, C., Kang, J., Chung Dai H., Freund J., and Evers B.M. Down-regulation of the tumor suppressor PTEN by the tumor necrosis factor-/nuclear factor-${\kappa}B$ (NF-${\kappa}B$)-inducing kinase/NF-${\kappa}B$ pathway is linked to a default I-eB-autoregulatory loop. J. Biol. Chem. 279, 4285-4291 (2004) https://doi.org/10.1074/jbc.M308383200
  14. Lee, Y.R, Shim, H.J., Yu, H.N., Song, E.K., Park, J., Kwon, K.B., Park, J.W., Rho, H.W., Park, B.H., Han, M.K., and Kim, J.S. Dimethylsulfoxide induces upregulation of tumor suppressor protein PTEN through nuclear factor-kappaB activation in HL-60 cells. Leuk. Res. 29, 401-405 (2005) https://doi.org/10.1016/j.leukres.2004.09.010
  15. Arch, R.H. and Thompson, C.B. Lymphocyte survival--the struggle against. Annu. Rev. Cell Dev. Biol. 15, 113-114 (1999) https://doi.org/10.1146/annurev.cellbio.15.1.113
  16. Locksley, R.M., Killeen, N., and Lenardo M.J. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell 104, 487-501 (2001) https://doi.org/10.1016/S0092-8674(01)00237-9
  17. Peraldi, P. and Spiegelman, B. TNF-alpha and insulin resistance: summary and future prospects. Mol. Cell. Biochem. 182, 169-175 (1998) https://doi.org/10.1023/A:1006865715292
  18. Chae, G.N. and Kwak, S.J. NF-${\kappa}B$ is involved in the TNF-a induced inhibition of the differentiation of 3T3-L1 cells by reducing PPARg expression. Exp. Mol. Med. 35, 431-437 (2003) https://doi.org/10.1038/emm.2003.56
  19. Hsu, H., Huang, J., Shu, H.B., Baichwal, V., and Goeddel, D.V. TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. Immunity 4, 387-396 (1996) https://doi.org/10.1016/S1074-7613(00)80252-6
  20. Hsu, H., Shu, H.B., Pan, M.G., and Goeddel, D.V. TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84, 299-308 (1996) https://doi.org/10.1016/S0092-8674(00)80984-8
  21. Hsu, H, Xiong, J, and Goeddel, DV. The TNF receptor 1-associated protein TRADD signals cell death and NF-kappa B activation. Cell 81, 495-504 (1995) https://doi.org/10.1016/0092-8674(95)90070-5
  22. Gribanova, N.V., Rakitina, T.V., Zhokhov, S.S., Pustoshilova, N.M., Lipkin, V.M., and Kostanian, I.A. Lglutamic acid modulates the cytotoxic effect of tumor necrosis factor in the HL-60 cell line. Bioorg. Khim. 31, 602-608 (2005)
  23. Karin, M., and Lin, A. NF-kappaB at the crossroads of life and death. Nat. Immunol. 3, 221-227 (2002) https://doi.org/10.1038/ni0302-221
  24. Wang, P., McKay, B.S., Allen, J.B., and Jaffe, G.J. Effect of NF-kB inhibition on TNF-a -induced apoptosis. Invest. Ophthalmol. Vis. Sci. 45, 2438-2446 (2004) https://doi.org/10.1167/iovs.03-0805
  25. Chen, C., Edlstein, L.C., and Gelinas, C. The Rel/NF-kB family directly activates expression of the apoptosis inhibitor Bcl-x(L). Mol. Cell. Biol. 20, 2687-2695 (2000) https://doi.org/10.1128/MCB.20.8.2687-2695.2000
  26. Stehlik, C., de Martin R., Kumabashiri, I., Schmid, J.A., Binder, B.R., and Lipp, J. Nuclear factor (NF)-kappa Bregulated X-chromosome-linked iap gene expression protects endothelial cells from tumor necrosis factor alpha-induced apoptosis. J Exp Med. 188, 211-216 (1998) https://doi.org/10.1084/jem.188.1.211
  27. Wang, C.Y., Mayo, M.W., Korneluk, R.G., Goeddel, D.V., and Baldwin, Jr A.S. NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP and c-IAP2 to suppress caspase-8 activation. Science 281, 1680-1683 (1998) https://doi.org/10.1126/science.281.5383.1680
  28. Berg, A.A, and Baltimore, D. An essential role for NF-kB in preventing TNF-a-induced cell death. Science 274, 782-274 (1996) https://doi.org/10.1126/science.274.5288.782
  29. Wang, C.Y., Mayo, M.W., and Baldwin, Jr A.S. TNF-and cancer therapy-induced apoptosis: potenitation by inhibition of NF-kappaB. Science 274, 784-787 (1996) https://doi.org/10.1126/science.274.5288.784
  30. Van Antewerp, D.J., Martin, S.J., Kafri, T, Green, D.R., and Verma, I.M. Suppression of TNF-a-induced apoptosis by NF-kB. Science 274, 787-789 (1996) https://doi.org/10.1126/science.274.5288.787
  31. Vasudevan, K.M., Gurumurthy, S., and Rangnekar V.M. Suppression of PTEN expression by NF-kB prevents apoptosis. Mol. Cell. Biol. 24,1007-1021 (2004) https://doi.org/10.1128/MCB.24.3.1007-1021.2004
  32. Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248-254 (1976) https://doi.org/10.1016/0003-2697(76)90527-3
  33. Cappellini, A., Tabellini, G., Zweyer, M., Bortul, R., Tazzari, P.L., Billi, A.M., Fala, F., Cocco, L., and Martelli, A.M. The phosphoinositide 3-kinase/Akt pathway regulates cell cycle progression of HL60 human leukemia cells through cytoplasmic relocalization of the cyclin-dependent kinase inhibitor p27(Kip1) and control of cyclin D1 expression. Leukemia 17, 2157-2167 (2003) https://doi.org/10.1038/sj.leu.2403111
  34. Altucci, L., Rossin, A., Raffelsberger, W., Reitmair, A., Chomienne, C., and Gronemeyer, H. Retinoic acid-induced apoptosis in leukemia cells is mediated by paracrine action of tumor-selective death ligand TRAIL. Nat. Med.7, 680-686 (2001) https://doi.org/10.1038/89050
  35. Hisatake, J., O'Kelly, J., Uskokovic, M.R., Tomoyasu, S., and Koeffler, H.P. Novel vitamin D(3) analog, 21-(3-methyl-3-hydroxy-butyl)-19-nor D(3), that modulates cell growth, differentiation, apoptosis, cell cycle, and induction of PTEN in leukemic cells. Blood 97, 2427-2433 (2001) https://doi.org/10.1182/blood.V97.8.2427
  36. DiDonato, J.A., Hayakawa, M., Rothwarf, D.M., Zandi, E., and Karin, M. A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB. Nature 388, 548-554 (1997) https://doi.org/10.1038/41493
  37. Mercurio, F., Zhu, H., Murray, B.W., Shevchenko, A., Bennett, B.L., Li, J., Young, D.B., Barbosa, M., Mann, M., Manning, A., and Rao, A. IKK-1 and IKK-2: cytokineactivated IkappaB kinases essential for NF-kappaB activation. Science 278, 860-866 (1997) https://doi.org/10.1126/science.278.5339.860