Faculty Collaboration Database

Interleukin-1beta can mediate growth arrest and differentiation via the leukemia inhibitory factor/JAK/STAT pathway in medullary thyroid carcinoma cells. Cytokine 2005 Feb 07;29(3):125-34

Date

12/23/2004

Pubmed ID

15613280

DOI

10.1016/j.cyto.2004.10.005

Scopus ID

2-s2.0-11144277904 (requires institutional sign-in at Scopus site)   28 Citations

Abstract

Interleukin-1beta (IL-1beta) is a pleiotropic cytokine that can induce several cellular signal transduction pathways. Here, we show that IL-1beta can induce cell cycle arrest and differentiation in the human medullary thyroid carcinoma (MTC) cell line, TT. IL-1beta induces cell cycle arrest accompanied by morphological changes and expression of the neuroendocrine marker calcitonin. These changes are blocked by the MEK1/2 specific inhibitor U0126, indicating that MEK1/2 is essential for IL-1beta signaling in TT cells. IL-1beta induces expression of leukemia inhibitory factor (LIF) and activation of STAT3 via the MEK/ERK pathway. This activation of STAT3 could be abrogated by treatment with anti-LIF neutralizing antibody or anti-gp130 blocking antibody, indicating that induction of LIF expression is sufficient and essential for STAT3 activation by IL-1beta. In addition to activation of the LIF/JAK/STAT pathway, IL-1beta also induced an MEK/ERK-mediated intracellular cell-autonomous signaling pathway that is independently sufficient for growth arrest and differentiation. Thus, IL-1beta activates the MEK/ERK pathway to induce growth arrest and differentiation in MTC cells via dual independent signaling mechanisms, the cell-extrinsic LIF/JAK/STAT pathway, and the cell-intrinsic autonomous signaling pathway.

Author List

Park JI, Strock CJ, Ball DW, Nelkin BD

Author

Jong-In Park PhD Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antigens, CD
Carcinoma, Medullary
Cell Differentiation
Cytokine Receptor gp130
DNA-Binding Proteins
Extracellular Signal-Regulated MAP Kinases
Humans
Interleukin-1
Interleukin-6
Janus Kinase 3
Leukemia Inhibitory Factor
MAP Kinase Kinase Kinase 1
MAP Kinase Kinase Kinase 2
Membrane Glycoproteins
Protein-Tyrosine Kinases
Proteins
STAT3 Transcription Factor
Signal Transduction
Thyroid Neoplasms
Trans-Activators