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Cited by 62Cytokine Signaling Pathways and InteractionsPancreatic and Hepatic Oncology ResearchSignaling Pathways in Disease

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

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Block, Katherine M., Hanke, Neale T., Maine, Erin A., Baker, Amanda F.·2012·Pancreas
DOI 10.1097/mpa.0b013e31823cdd10PMC PMC3337960
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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.

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  • The IL-6-STAT3-Pim kinase axis is involved in the development and cell growth of pancreatic cancer.

    “The IL-6–STAT3–Pim kinase axis is involved in the development and cell growth of pancreatic cancer (128, 129).”

    From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [128]

    The Introduction and Discussion (page unavailable) support a role for IL-6–STAT3 signaling in pancreatic cancer and report that IL-6 increases Pim-1 expression. But the Discussion reports no increased proliferation after IL-6 stimulation, and the Results found no significant growth difference with Pim-1 overexpression. The paper therefore does not establish that the full axis promotes pancreatic cancer cell growth; it describes Pim-1’s effects as context dependent. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Block, K. M., Hanke, N. T., Maine, E. A., & Baker, A. F.
Affiliations
University of Arizona Cancer Center (US)
ORCID
Baker, Amanda F.
Venue
Pancreas
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2012-07
Volume
41
Issue
5
Pages
773-781
ISSN
0885-3177 (ISSN-L)
DOI
10.1097/mpa.0b013e31823cdd10
PMC
PMC3337960
OpenAlex
W1967809346
Cited by
62
References
1
Citations by year
2026: 2 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 6 · 2017: 5 · 2016: 6 · 2015: 6 · 2014: 7 · 2013: 5
FWCI
2.85
Type
journal article
Language
en
Open access
Locations
  • Pancreas (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (P50 CA95060, P01CA017094, CA017094, P50CA095060, P30CA023074)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
interleukin-6, STAT3, PIM-1, pancreatic cancer, IL-6 receptor, cucurbitacin I, ERK1/2 phosphorylation, tumor growth, PANC-1 cells, MIA PaCa-2 cells
MeSH terms
Proto-Oncogene Mas, Animals, Humans, Male, Pancreatic Neoplasms, Transplantation, Heterologous, Triterpenes, Blotting, Western, Interleukin-6, Gene Expression Regulation, Neoplastic, Mice, SCID, Apoptosis, Receptors, Interleukin-6, Mitogen-Activated Protein Kinase 1, Reverse Transcriptase Polymerase Chain Reaction, Cell Line, Tumor, Tumor Burden, Mitogen-Activated Protein Kinase 3, Cell Proliferation, STAT3 Transcription Factor, Mice, Proto-Oncogene Proteins c-pim-1

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