TY - JOUR
T1 - LTB4 stimulates growth of human pancreatic cancer cells via MAPK and PI-3 kinase pathways
AU - Tong, Wei Gang
AU - Ding, Xian Zhong
AU - Talamonti, Mark S.
AU - Bell, Richard H.
AU - Adrian, Thomas E.
N1 - Funding Information:
These studies were supported by grants from the NCI SPORE program (P50 CA72712) and the Lustgarten Foundation for Pancreatic Cancer Research. The selective LTB4 receptor antagonist, LY293111, was a kind gift from Drs. Jake Starling and Jerome Fleisch, Eli Lilly Research Laboratories (Indianapolis, IN).
PY - 2005/9/30
Y1 - 2005/9/30
N2 - We have previously shown the importance of LTB4 in human pancreatic cancer. LTB4 receptor antagonists block growth and induce apoptosis in pancreatic cancer cells both in vitro and in vivo. Therefore, we investigated the effect of LTB4 on proliferation of human pancreatic cancer cells and the mechanisms involved. LTB4 stimulated DNA synthesis and proliferation of both PANC-1 and AsPC-1 human pancreatic cancer cells, as measured by thymidine incorporation and cell number. LTB4 stimulated rapid and transient activation of MEK and ERK1/2 kinases. The MEK inhibitors, PD98059 and U0126, blocked LTB4-stimulated ERK1/2 activation and cell proliferation. LTB4 also stimulated phosphorylation of p38 MAPK; however, the p38 MAPK inhibitor, SB203580, failed to block LTB4-stimulated growth. The activity of JNK/SAPK was not affected by LTB4 treatment. Phosphorylation of Akt was also induced by LTB4 and this effect was blocked by the PI-3 kinase inhibitor wortmannin, which also partially blocked LTB4-stimulated cell proliferation. In conclusion, LTB4 stimulates proliferation of human pancreatic cancer cells through MEK/ERK and PI-3 kinase/Akt pathways, while p38 MPAK and JNK/SAPK are not involved.
AB - We have previously shown the importance of LTB4 in human pancreatic cancer. LTB4 receptor antagonists block growth and induce apoptosis in pancreatic cancer cells both in vitro and in vivo. Therefore, we investigated the effect of LTB4 on proliferation of human pancreatic cancer cells and the mechanisms involved. LTB4 stimulated DNA synthesis and proliferation of both PANC-1 and AsPC-1 human pancreatic cancer cells, as measured by thymidine incorporation and cell number. LTB4 stimulated rapid and transient activation of MEK and ERK1/2 kinases. The MEK inhibitors, PD98059 and U0126, blocked LTB4-stimulated ERK1/2 activation and cell proliferation. LTB4 also stimulated phosphorylation of p38 MAPK; however, the p38 MAPK inhibitor, SB203580, failed to block LTB4-stimulated growth. The activity of JNK/SAPK was not affected by LTB4 treatment. Phosphorylation of Akt was also induced by LTB4 and this effect was blocked by the PI-3 kinase inhibitor wortmannin, which also partially blocked LTB4-stimulated cell proliferation. In conclusion, LTB4 stimulates proliferation of human pancreatic cancer cells through MEK/ERK and PI-3 kinase/Akt pathways, while p38 MPAK and JNK/SAPK are not involved.
KW - Extracellular regulated kinase
KW - Leukotriene B4
KW - Mitogen activated protein kinase
KW - Pancreatic cancer
KW - Phosphoinositol-3 kinase
KW - Protein kinase B
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U2 - 10.1016/j.bbrc.2005.07.166
DO - 10.1016/j.bbrc.2005.07.166
M3 - Article
C2 - 16105664
AN - SCOPUS:23944483974
SN - 0006-291X
VL - 335
SP - 949
EP - 956
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -