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 language | English (US) |
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Pages (from-to) | 1365-1370 |
Number of pages | 6 |
Journal | Oncogene |
Volume | 22 |
Issue number | 9 |
DOIs | |
State | Published - Mar 6 2003 |
Externally published | Yes |
Keywords
- Angiogenesis
- IκBα
- NF-κB
- Pancreatic cancer
- Tumorigenesis
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research