Correlation between the Expression of Nuclear Factor-$\kappa$B p65 Protein with the Expression of Nuclear Factor-$\kappa$B p50 Protein and the Clinicopathologic Factors in Colorectal Cancer

결장직장암에서 Nuclear Factor-$\kappa$B p65와 Nuclear Factor-$\kappa$B p50 단백 발현과 임상병리학 인자와의 연관성

Kang, Gi-Chang;Kim, Beom-Gyu;Park, Jun-Suk;Choi, Yu-Sin;Cha, Sung-Jae;Park, Sung-Jun;Chang, In-Taik;Park, Sung-Il;Lee, Tae-Jin;Choi, Young-Cheol
강기창;김범규;박준석;최유신;차성재;박성준;장인택;박성일;이태진;최영철

  • Published : 20080800

Abstract

Purpose: Nuclear Factor-κB p65 (NF-κB p65) and nuclear Factor-κB1 p50 (NF-κB p65) have been shown to play roles in cell proliferation, apoptosis, cytokine production and oncogenesis. This study was designed to investigate the expressions of NF-κB p65 and NF-κB p50 proteins in premalignant lesions and colorectal adenocarcinoma. Methods: Paraffin sections of 20 normal mucosa specimens, 20 low grade tubular adenoma specimens, 20 high grade tubular adenoma specimens and 64 adenocarcinoma specimens were analyzed immunohistochemically for the expressions of NF-κB p65 and NF-κB p50 proteins. Results: The expressions of NF-κB p65 and NF-κB p50 proteins were significantly higher in the adenocarcinoma tissue compared with that in the normal mucosa, the low grade tubular adenoma and the high grade tubular adenoma tissues. The frequency of a NF-κB p50 expression was higher in the poorly differentiated histologic grade specimens, in the presence of nodal metastasis and in the high stage specimens. There were significant correlations between the NF-κB p65 and NF-κB p50 proteins. Conclusion: The expressions of NF-κB p65 and NF-κB p50 proteins may play a role in the pathogenesis of colorectal carcinoma. (J Korean Surg Soc 2008;75:84-89)

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References

  1. Lind DS, Hochwald SN, Malaty J, Rekkas S, Hebig P, Mishra G, et al. Nuclear factor-kappa B is upregulated in colorectal cancer. Surgery 2001;130:363-9. https://doi.org/10.1067/msy.2001.116672
  2. 2006 Korean cancer research 2007. Ministry of health and welfare, Korea.
  3. Aranha MM. NF-kappaB and apoptosis in colorectal tumourigenesis. Eur J Clin Invest 2007;37:416-24. https://doi.org/10.1111/j.1365-2362.2007.01801.x
  4. Karin M. NF-${\kappa}B$ and cancer: mechanism and targets. Mol Carcinogenesis 2006;45:355-61. https://doi.org/10.1002/mc.20217
  5. Xiao CW, Yan X, Li Y, Reddy SA, Tsang BK. Resistance of human ovarian cancer cells to tumor necrosis factor alpha is a consequence of nuclear factor kappaB-mediated induction of Fas-associated death domain-like interleukin-1beta- converting enzyme-like inhibitory protein. Endocrinology 2003;144:623-30. https://doi.org/10.1210/en.2001-211024
  6. Mukhopadhyay T, Roth JA, Maxwell SA. Altered expression of the p50 subunit of the NF-${\kappa}B$ transcription factor complex in non-small cell lung carcinoma. Oncogene 1995;11:999-1003.
  7. Nakshatri H, Bhat-Nakshatri P, Martin DA, Goulet RJ Jr, Sledge GW Jr. Constitutive activation of NF-${\kappa}B$ during progression of breast cancer to hormone-independent growth. Mol Cell Biol 1997;17:3629-39. https://doi.org/10.1128/MCB.17.7.3629
  8. Visconti R, Cerutti J, Battista S, Fedele M, Trapasso F, Zeki K, et al. Expression of the neoplastic phenotype by human thyroid carcinoma cell lines requires NF-${\kappa}B$ p65 protein expression. Oncogene 1997;15:1987-94. https://doi.org/10.1038/sj.onc.1201373
  9. Ivanov VN, Bhoumik A, Ronai Z. Death receptors and melanoma resistance to apoptosis. Oncogene 2003;22:3152-61. https://doi.org/10.1038/sj.onc.1206456
  10. Sumitomo M, Tachibana M, Ozu C, Asakura H, Murai M, Hayakawa M, et al. Induction of apoptosis of cytokine-producing bladder cancer cells by adenovirus-mediated I${\kappa}B$ overexpression. Hum Gene Ther 1999;10:37-47. https://doi.org/10.1089/10430349950019174
  11. Karin M. NF-${\kappa}B$ and cancer: Mechanism and targets. Mol carcinog 2006;45:355-61. https://doi.org/10.1002/mc.20217
  12. Loncar MB, Al-Azzeh ED, Sommer PS, Marinovic M, Schmehl K, Kruschewski M, et al. Tumour necrosis factor alpha and nuclear factor kappaB inhibit transcription of human TFF3 encoding a gastrointestinal healing peptide. Gut 2003;52:1297-303. https://doi.org/10.1136/gut.52.9.1297
  13. Ghosh S, May MJ, Kopp EB. NF-${\kappa}B$ and Rel proteins: evolutionarily conserved mediators of immune responses. Annu Rev Immunol 1998;16:225-60 https://doi.org/10.1146/annurev.immunol.16.1.225
  14. Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 2003; 114:181-90 https://doi.org/10.1016/S0092-8674(03)00521-X
  15. Siebenlist U, Franzoso G, Brown K. Structure, regulation and function of NF-${\kappa}B$. Annu Rev Cell Biol 1994;10:405-55. https://doi.org/10.1146/annurev.cb.10.110194.002201
  16. Bargou RC, Leng C, Krappmann D, Emmerich F, Mapara MY, Bommert K, et al. High-level nuclear NF-${\kappa}B$ and Oct-2 is a common feature of cultured Hodgkin/ Reed-Sternberg cells. Blood 1996;87:4340-7.
  17. Giri DK, Aggarwal BB. Constitutive activation of NF-${\kappa}B$ causes resistance to apoptosis in human cutaneous T cell lymphoma HuT-78 cells. Autocrine role of tumor necrosis factor and reactive oxygen intermediates. J Biol Chem 1998;273:14008-14. https://doi.org/10.1074/jbc.273.22.14008
  18. Feinman R, Koury J, Thames M, Barlogie B, Epstein J, Siegel DS. Role of NF-kappaB in the rescue of multiple myeloma cells from glucocorticoid-induced apoptosis by bcl-2. Blood 1999;93:3044-52.
  19. Yu LL, Yu HG, Yu JP, Luo HS, Xu XM, Li JH. Nuclear factor- ${\kappa}B$ p65 (RelA) transcription factor is constitutively activated in human colorectal carcinoma tissue. World J Gastroenterol 2004;10:3255-60. https://doi.org/10.3748/wjg.v10.i22.3255
  20. Aranha MM, Borralho PM, Ravasco P, Moreira da silva IB, Correia L, Fernandes A, et al. NF-${\kappa}B$ and apoptosis in colorectal carcinoma. Eur Clin Invest 2007;37:416-24. https://doi.org/10.1111/j.1365-2362.2007.01801.x
  21. Karin M, Lin A. NF-${\kappa}B$ at the crossroads of life and death. Nat Immunol 2002;3:221-7. https://doi.org/10.1038/ni0302-221
  22. Karin M, Yamamoto Y, Wang QM. The IIK NF-${\kappa}B$ system: a treasure trove for drug development. Nat Rev Drug Discov 2004;3:17-26. https://doi.org/10.1038/nrd1279