Nuclear factor κB activity correlates with the progression and prognosis of pancreatic cancer in a mouse model.

Abstract

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.

• Authors: Kenei Furukawa, Tadashi Uwagawa, Koichiro Haruki, Yuki Fujiwara, Tomonori Iida, Hiroaki Shiba, Takeyuki Misawa, Toya Ohashi, Katsuhiko Yanaga
• Journal: Surgery today (Surg Today) Vol. 43 Issue 2 Pg. 171-7 (Feb 2013) ISSN: 1436-2813 [Electronic] Japan
• PMID: 22892758 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• Transcription Factor RelA

Topics

• Animals
• Biomarkers, Tumor (metabolism)
• Cell Line, Tumor
• Disease Progression
• Enzyme-Linked Immunosorbent Assay
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness
• Pancreatic Neoplasms (metabolism, mortality, pathology)
• Prognosis
• Survival Analysis
• Transcription Factor RelA (metabolism)