INTRODUCTION: Constitutive NF-κB activation is considered to play a key role in the aggressive behavior of pancreatic cancer. Although NF-κB in tumors may contribute to aggressive characteristic features via transcription of angiogenesis and invasion-related factors, there is no definitive evidence showing a correlation between quantitated NF-κB activity and prognosis. In this study, we quantitated NF-κB activity of various human pancreatic cancer cell lines and evaluated whether NF-κB activity was related to tumor progression and prognosis for pancreatic cancer in mice. MATERIALS AND METHODS: We quantitated NF-κB activity in six pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-2, MIAPaCa-2, Panc-1 and PL45) and evaluated downstream target genes of NF-κB such as VEGF, IL-8 and MMP-9 in vitro. Next, we evaluated tumor progression and prognosis using subcutaneous tumor model in vivo between cell lines with the highest and lowest NF-κB activity. RESULTS: BxPC-3 had the highest and AsPC-1 had the lowest NF-κB activity in the 6 cell lines. Expression of VEGF, IL-8 and MMP-9 in BxPC-3 was significantly higher than those in AsPC-1 cells in vitro (p < 0.001) and tumor growth in BxPC-3 was faster than that in AsPC-1 group (p < 0.001) resulting in worse survival in vivo (p = 0.0339). CONCLUSION: These results suggested that NF-κB activity is related to expression of its downstream target genes, tumor progression and prognosis in experimental pancreatic cancer model.
INTRODUCTION: Constitutive NF-κB activation is considered to play a key role in the aggressive behavior of pancreatic cancer. Although NF-κB in tumors may contribute to aggressive characteristic features via transcription of angiogenesis and invasion-related factors, there is no definitive evidence showing a correlation between quantitated NF-κB activity and prognosis. In this study, we quantitated NF-κB activity of various humanpancreatic cancer cell lines and evaluated whether NF-κB activity was related to tumor progression and prognosis for pancreatic cancer in mice. MATERIALS AND METHODS: We quantitated NF-κB activity in six pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-2, MIAPaCa-2, Panc-1 and PL45) and evaluated downstream target genes of NF-κB such as VEGF, IL-8 and MMP-9 in vitro. Next, we evaluated tumor progression and prognosis using subcutaneous tumor model in vivo between cell lines with the highest and lowest NF-κB activity. RESULTS: BxPC-3 had the highest and AsPC-1 had the lowest NF-κB activity in the 6 cell lines. Expression of VEGF, IL-8 and MMP-9 in BxPC-3 was significantly higher than those in AsPC-1 cells in vitro (p < 0.001) and tumor growth in BxPC-3 was faster than that in AsPC-1 group (p < 0.001) resulting in worse survival in vivo (p = 0.0339). CONCLUSION: These results suggested that NF-κB activity is related to expression of its downstream target genes, tumor progression and prognosis in experimental pancreatic cancer model.
Authors: Jordan D Berlin; Paul Catalano; James P Thomas; John W Kugler; Daniel G Haller; Al Bowen Benson Journal: J Clin Oncol Date: 2002-08-01 Impact factor: 44.544
Authors: Navneet Dhillon; Bharat B Aggarwal; Robert A Newman; Robert A Wolff; Ajaikumar B Kunnumakkara; James L Abbruzzese; Chaan S Ng; Vladimir Badmaev; Razelle Kurzrock Journal: Clin Cancer Res Date: 2008-07-15 Impact factor: 12.531