LTB4 stimulates growth of human pancreatic cancer cells via MAPK and PI-3 kinase pathways

Journal Article · Fri Sep 30 00:00:00 EDT 2005 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2005.07.166· OSTI ID:20711002

Tong, W -G ^[1]; Ding, X -Z ^[1]; Talamonti, Mark S ^[1]; Bell, Richard H ^[1]; Adrian, Thomas E ^[1]

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1. Department of Surgery and Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611 (United States)

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.

• OSTI ID: 20711002
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 335, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2005.07.166; PII: S0006-291X(05)01672-4; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CELL PROLIFERATION
DNA
GROWTH
IN VITRO
IN VIVO
NEOPLASMS
PANCREAS
PHOSPHORYLATION
PHOSPHOTRANSFERASES
RECEPTORS
THYMIDINE