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


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).


CONCLUSIONS
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.
Department of Surgery, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461, Japan. k-furukawa@jikei.ac.jp
Kenei
K
Furukawa
Tadashi
T
Uwagawa
Koichiro
K
Haruki
Yuki
Y
Fujiwara
Tomonori
T
Iida
Hiroaki
H
Shiba
Takeyuki
T
Misawa
Toya
T
Ohashi
Katsuhiko
K
Yanaga
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D051996:Transcription Factor RelA / Q000378:metabolism*
D014408:Biomarkers, Tumor; D051996:Transcription Factor RelA