Interleukin-9 (IL-9) induces cell growth arrest associated with sustained signal transducer and activator of transcription activation in lymphoma cells overexpressing the IL-9 receptor.

Abstract

Murine interleukin (IL)-9 inhibits apoptosis in murine T lymphomas via signal transducer and activator of transcription (STAT) factors. After transfection of the human IL-9 receptor, human IL-9 had a similar antiapoptotic activity, but, unlike the mouse protein, inhibited proliferation. This effect was correlated with the level of receptor expression and the extent of STAT phosphorylation. Expression of a moderate level of suppressor of cytokine signaling 3 (SOCS3) reduced STAT activation by human IL-9 and prevented inhibition of growth but not of apoptosis. Using mutated IL-9 receptors, we showed that inhibition of proliferation was correlated with STAT1 and STAT3 activation by IL-9 and induction of the cell cycle inhibitor p19/ink4d, a STAT3 target gene. Activation of STAT1 by IFN-gamma did not result in cell growth arrest. In this model, cell growth inhibition is therefore associated with a higher number of receptors, a more robust STAT activation, and a greater sensitivity to SOCS3 expression, compared to apoptosis inhibition.

• Authors: J B Demoulin, J Van Snick, J C Renauld
• Journal: Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research (Cell Growth Differ) Vol. 12 Issue 3 Pg. 169-74 (Mar 2001) ISSN: 1044-9523 [Print] United States
• PMID: 11306517 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Cdkn2d protein, mouse
• Cell Cycle Proteins
• Cyclin-Dependent Kinase Inhibitor p16
• Cyclin-Dependent Kinase Inhibitor p19
• DNA-Binding Proteins
• IL9R protein, human
• Interleukin-9
• Milk Proteins
• Receptors, Interleukin
• Receptors, Interleukin-9
• STAT1 Transcription Factor
• STAT3 Transcription Factor
• STAT5 Transcription Factor
• Stat1 protein, mouse
• Stat3 protein, mouse
• Trans-Activators

Topics

• Animals
• Apoptosis (drug effects, physiology)
• Carrier Proteins (drug effects, metabolism)
• Cell Cycle Proteins
• Cell Division (drug effects, physiology)
• Cyclin-Dependent Kinase Inhibitor p16
• Cyclin-Dependent Kinase Inhibitor p19
• DNA-Binding Proteins (drug effects, metabolism)
• Gene Expression Regulation, Neoplastic (drug effects, physiology)
• Interleukin-9 (pharmacology)
• Lymphoma (drug therapy, metabolism, physiopathology)
• Lymphoma, T-Cell (drug therapy, metabolism, physiopathology)
• Mice
• Milk Proteins
• Receptors, Interleukin (drug effects, metabolism)
• Receptors, Interleukin-9
• STAT1 Transcription Factor
• STAT3 Transcription Factor
• STAT5 Transcription Factor
• Signal Transduction (drug effects, physiology)
• Trans-Activators (drug effects, metabolism)
• Transcription, Genetic (drug effects, physiology)
• Tumor Cells, Cultured (cytology, drug effects, metabolism)