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Updated: Aug 19, 2026
Simulating Pancreatic Neuroplasticity: In Vitro Dual-neuron Plasticity Assay
Published on: April 15, 2014
Glial cell line-derived neurotrophic factor enhances nuclear factor-kappaB activity and invasive potential in human
Hiroki Takahashi1, Hitoshi Funahashi, Hirozumi Sawai
1Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. takahasi@med.nagoya-cu.ac.jp
Objectives:
The invasive potential is increased by glial cell line-derived neurotrophic factor (GDNF) in human pancreatic cancer cell lines. We researched whether the signaling pathway activated by GDNF correlates with the nuclear factor-kappaB (NF-kappaB) in human pancreatic cancer cell lines and whether the inhibition of NF-kappaB activity is associated with suppression of invasive potential.
Methods:
Proliferation of human pancreatic cancer cell lines (BxPC-3 and MIA PaCa-2) was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays (MTT assay). NF-kappaB activity was examined by dual luciferase assay and electrophoretic mobility shift assay. In addition, to investigate the invasive potential, an in vitro invasion assay was performed.
Results:
Proliferation of both cell lines was decreased by a proteasome inhibitor, MG132, in a dose-dependent manner, but proliferation of control and IkappaBalphaM vector-transfected BxPC-3 cells was similar. The invasion cell number and the NF-kappaB activity were increased by GDNF stimulation. However, in the presence of MG132 or IkappaBalphaM, which blocks the nuclear localization of NF-kappaB, both were significantly suppressed. Furthermore, reduced activity of both remained unchanged by GDNF stimulation.
Conclusion:
These results indicate that GDNF promotes NF-kappaB activation and that the latter is involved in the invasive potential of human pancreatic cancer cells.
