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- Title
Inhibition of constitutive NF-?B activity by I?BaM suppresses tumorigenesis.
- Authors
Fujioka, Shuichi; Sclabas, Guido M; Schmidt, Christian; Niu, Jiangong; Frederick, Wayne A; Dong, Qiang G; Abbruzzese, James L; Evans, Douglas B; Baker, Cheryl; Chiao, Paul J
- Abstract
We have demonstrated that nuclear factor-?B (NF-?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-?B plays a critical role in the development of pancreatic adenocarcinoma. To elucidate the role of constitutive NF-?B activity in human pancreatic cancer cells, we generated pancreatic tumor cell lines that express a phosphorylation defective I?Ba (S32, 36A) (I?BaM) that blocks NF-?B activity. In this study, we showed that inhibiting constitutive NF-?B activity by expressing I?BaM 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-?B signaling by expressing I?BaM 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-?B signaling can suppress tumorigenesis of pancreatic cancer cells and that the NF-?B signaling pathway is a potential target for anticancer agents.Oncogene (2003) 22, 1365-1370. doi:10.1038/sj.onc.1206323
- Subjects
NF-kappa B; CARCINOGENESIS; TUMOR suppressor genes; NEOVASCULARIZATION inhibitors
- Publication
Oncogene, 2003, Vol 22, Issue 9, p1365
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1206323