IL-6 stimulates STAT3 and Pim-1 kinase in pancreatic cancer cell lines.

Abstract

OBJECTIVES:

We investigated the signaling pathways activated in response to interleukin 6 (IL-6) in pancreatic cell lines, with a focus on signal transducer and activator of transcription 3 (STAT3) and proto-oncogene serine/threonine-protein (Pim-1) kinase.

METHODS:

Interleukin 6 receptor (IL-6R) expression and IL-6-induced cell signaling was measured by Western blotting in human pancreatic cell lines. Cucurbitacin I was used as a pharmacological tool to investigate the role of STAT3 in Pim-1 activation. Stably overexpressing Pim-1 kinase cell lines were characterized for their response to IL-6 in vitro and for their growth rate as flank tumors in scid mice.

RESULTS:

Interleukin 6 receptor was expressed across multiple cancer cell lines. In Panc-1 cells, IL-6 treatment increased expression of phosphorylation of signal transducer and activator of transcription 3 and Pim-1 kinase. Cucurbitacin I treatment alone increased pErk1/2 expression in wild-type and Pim-1-overexpressing cell lines and resulted in exaggerated Pim-1 kinase protein levels in control and IL-6-stimulated cells, suggesting that up-regulation of Pim-1 may be partially STAT3 independent. Pim-1 overexpression did not significantly affect growth rate in vitro or in vivo in Panc-1 or MiaPaCa2 cell lines.

CONCLUSIONS:

Interleukin 6 activates STAT3 and stimulates Pim-1 kinase in pancreatic cell line models. The regulation and consequence of Pim-1 expression seems to be highly context dependent.

• Authors: Katherine M Block, Neale T Hanke, Erin A Maine, Amanda F Baker
• Journal: Pancreas (Pancreas) Vol. 41 Issue 5 Pg. 773-81 (Jul 2012) ISSN: 1536-4828 [Electronic] United States
• PMID: 22273698 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Interleukin-6
• MAS1 protein, human
• Proto-Oncogene Mas
• Receptors, Interleukin-6
• STAT3 Transcription Factor
• Triterpenes
• Proto-Oncogene Proteins c-pim-1
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• cucurbitacin I

Topics

• Animals
• Apoptosis (drug effects)
• Blotting, Western
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Interleukin-6 (pharmacology)
• Male
• Mice
• Mice, SCID
• Mitogen-Activated Protein Kinase 1 (genetics, metabolism)
• Mitogen-Activated Protein Kinase 3 (genetics, metabolism)
• Pancreatic Neoplasms (genetics, metabolism, pathology)
• Proto-Oncogene Mas
• Proto-Oncogene Proteins c-pim-1 (genetics, metabolism)
• Receptors, Interleukin-6 (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• STAT3 Transcription Factor (genetics, metabolism)
• Transplantation, Heterologous
• Triterpenes (pharmacology)
• Tumor Burden (genetics)