Inhibition of constitutive NF-κB activity by IκBαM suppresses tumorigenesis

Shuichi Fujioka, Guido M. Sclabas, Christian Schmidt, Jiangong Niu, Wayne A. Frederick, Qiang G. Dong, James L. Abbruzzese, Douglas B. Evans, Cheryl Baker, Paul J. Chiao

Research output: Contribution to journalArticle

Abstract

We have demonstrated that nuclear factor-κB (NF-κB) 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-κB plays a critical role in the development of pancreatic adenocarcinoma. To elucidate the role of constitutive NF-κB activity in human pancreatic cancer cells, we generated pancreatic tumor cell lines that express a phosphorylation defective IκBα (S32, 36A) (IκBαM) that blocks NF-κB activity. In this study, we showed that inhibiting constitutive NF-κB activity by expressing IκBαM 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-κB signaling by expressing IκBαM significantly reduced expression of Bcl-xL 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-κB signaling can suppress tumorigenesis of pancreatic cancer cells and that the NF-κB signaling pathway is a potential target for anticancer agents.

Original languageEnglish (US)
Pages (from-to)1365-1370
Number of pages6
JournalOncogene
Volume22
Issue number9
DOIs
StatePublished - Mar 6 2003

Keywords

  • Angiogenesis
  • IκBα
  • NF-κB
  • Pancreatic cancer
  • Tumorigenesis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Fujioka, S., Sclabas, G. M., Schmidt, C., Niu, J., Frederick, W. A., Dong, Q. G., Abbruzzese, J. L., Evans, D. B., Baker, C., & Chiao, P. J. (2003). Inhibition of constitutive NF-κB activity by IκBαM suppresses tumorigenesis. Oncogene, 22(9), 1365-1370. https://doi.org/10.1038/sj.onc.1206323