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Inhibition of constitutive NF-kappa B activity by I kappa B alpha M suppresses tumorigenesis.

Publication ,  Journal Article
Fujioka, S; Sclabas, GM; Schmidt, C; Niu, J; Frederick, WA; Dong, QG; Abbruzzese, JL; Evans, DB; Baker, C; Chiao, PJ
Published in: Oncogene
March 6, 2003

We have demonstrated that nuclear factor-kappa B (NF-kappa B) is constitutively activated in human pancreatic adenocarcinoma and human pancreatic cancer cell lines but not in normal pancreatic tissues or in immortalized, nontumorigenic pancreatic epithelial cells, suggesting that NF-kappa B plays a critical role in the development of pancreatic adenocarcinoma. To elucidate the role of constitutive NF-kappa B activity in human pancreatic cancer cells, we generated pancreatic tumor cell lines that express a phosphorylation defective I kappa B alpha (S32, 36A) (I kappa B alpha M) that blocks NF-kappa B activity. In this study, we showed that inhibiting constitutive NF-kappa B activity by expressing I kappa B alpha M suppressed the tumorigenicity of a nonmetastatic human pancreatic cancer cell line, PANC-1, in an orthotopic nude mouse model. Immunohistochemical analysis showed that PANC-1-derived tumors expressed vascular endothelial growth factor (VEGF) and induced angiogenesis. Inhibiting NF-kappa B signaling by expressing I kappa B alpha M significantly reduced expression of Bcl-x(L) and Bcl-2. The cytokine-induced expression of VEGF and Interleukin-8 in PANC-1 cells is also decreased. Taken together, these results suggest that the inhibition of NF-kappa B signaling can suppress tumorigenesis of pancreatic cancer cells and that the NF-kappa B signaling pathway is a potential target for anticancer agents.

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Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

March 6, 2003

Volume

22

Issue

9

Start / End Page

1365 / 1370

Location

England

Related Subject Headings

  • bcl-X Protein
  • Vascular Endothelial Growth Factors
  • Vascular Endothelial Growth Factor A
  • Tumor Necrosis Factor-alpha
  • Tumor Cells, Cultured
  • Recombinant Fusion Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Protein Processing, Post-Translational
  • Promoter Regions, Genetic
  • Phosphorylation
 

Citation

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Fujioka, S., Sclabas, G. M., Schmidt, C., Niu, J., Frederick, W. A., Dong, Q. G., … Chiao, P. J. (2003). Inhibition of constitutive NF-kappa B activity by I kappa B alpha M suppresses tumorigenesis. Oncogene, 22(9), 1365–1370. https://doi.org/10.1038/sj.onc.1206323
Fujioka, Shuichi, Guido M. Sclabas, Christian Schmidt, Jiangong Niu, Wayne A. Frederick, Qiang G. Dong, James L. Abbruzzese, Douglas B. Evans, Cheryl Baker, and Paul J. Chiao. “Inhibition of constitutive NF-kappa B activity by I kappa B alpha M suppresses tumorigenesis.Oncogene 22, no. 9 (March 6, 2003): 1365–70. https://doi.org/10.1038/sj.onc.1206323.
Fujioka S, Sclabas GM, Schmidt C, Niu J, Frederick WA, Dong QG, et al. Inhibition of constitutive NF-kappa B activity by I kappa B alpha M suppresses tumorigenesis. Oncogene. 2003 Mar 6;22(9):1365–70.
Fujioka, Shuichi, et al. “Inhibition of constitutive NF-kappa B activity by I kappa B alpha M suppresses tumorigenesis.Oncogene, vol. 22, no. 9, Mar. 2003, pp. 1365–70. Pubmed, doi:10.1038/sj.onc.1206323.
Fujioka S, Sclabas GM, Schmidt C, Niu J, Frederick WA, Dong QG, Abbruzzese JL, Evans DB, Baker C, Chiao PJ. Inhibition of constitutive NF-kappa B activity by I kappa B alpha M suppresses tumorigenesis. Oncogene. 2003 Mar 6;22(9):1365–1370.

Published In

Oncogene

DOI

ISSN

0950-9232

Publication Date

March 6, 2003

Volume

22

Issue

9

Start / End Page

1365 / 1370

Location

England

Related Subject Headings

  • bcl-X Protein
  • Vascular Endothelial Growth Factors
  • Vascular Endothelial Growth Factor A
  • Tumor Necrosis Factor-alpha
  • Tumor Cells, Cultured
  • Recombinant Fusion Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Protein Processing, Post-Translational
  • Promoter Regions, Genetic
  • Phosphorylation