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

Katherine M. Block, Neale T. Hanke, Erin A. Maine, Amanda F Baker

Research output: Contribution to journalArticle

35 Citations (Scopus)

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 protooncogene 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.

Original languageEnglish (US)
Pages (from-to)773-781
Number of pages9
JournalPancreas
Volume41
Issue number5
DOIs
StatePublished - Jul 2012

Fingerprint

Proto-Oncogene Proteins c-pim-1
STAT3 Transcription Factor
Pancreatic Neoplasms
Interleukin-6
Cell Line
Interleukin-6 Receptors
Threonine
Growth
Serine
Neoplasms
Proteins
Up-Regulation
Western Blotting
Phosphorylation
Pharmacology

Keywords

  • Interleukin 6
  • Pancreatic cancer
  • Pim-1 kinase
  • Signal transducer and activator of transcription 3

ASJC Scopus subject areas

  • Hepatology
  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

IL-6 stimulates STAT3 and Pim-1 kinase in pancreatic cancer cell lines. / Block, Katherine M.; Hanke, Neale T.; Maine, Erin A.; Baker, Amanda F.

In: Pancreas, Vol. 41, No. 5, 07.2012, p. 773-781.

Research output: Contribution to journalArticle

Block, Katherine M. ; Hanke, Neale T. ; Maine, Erin A. ; Baker, Amanda F. / IL-6 stimulates STAT3 and Pim-1 kinase in pancreatic cancer cell lines. In: Pancreas. 2012 ; Vol. 41, No. 5. pp. 773-781.
@article{877c33b8e7c3445794c2b67ad212c6b8,
title = "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 protooncogene 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.",
keywords = "Interleukin 6, Pancreatic cancer, Pim-1 kinase, Signal transducer and activator of transcription 3",
author = "Block, {Katherine M.} and Hanke, {Neale T.} and Maine, {Erin A.} and Baker, {Amanda F}",
year = "2012",
month = "7",
doi = "10.1097/MPA.0b013e31823cdd10",
language = "English (US)",
volume = "41",
pages = "773--781",
journal = "Pancreas",
issn = "0885-3177",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - IL-6 stimulates STAT3 and Pim-1 kinase in pancreatic cancer cell lines

AU - Block, Katherine M.

AU - Hanke, Neale T.

AU - Maine, Erin A.

AU - Baker, Amanda F

PY - 2012/7

Y1 - 2012/7

N2 - 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 protooncogene 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.

AB - 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 protooncogene 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.

KW - Interleukin 6

KW - Pancreatic cancer

KW - Pim-1 kinase

KW - Signal transducer and activator of transcription 3

UR - http://www.scopus.com/inward/record.url?scp=84863686744&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863686744&partnerID=8YFLogxK

U2 - 10.1097/MPA.0b013e31823cdd10

DO - 10.1097/MPA.0b013e31823cdd10

M3 - Article

VL - 41

SP - 773

EP - 781

JO - Pancreas

JF - Pancreas

SN - 0885-3177

IS - 5

ER -