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  • Title: 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.
    Author: Demoulin JB, Van Snick J, Renauld JC.
    Journal: Cell Growth Differ; 2001 Mar; 12(3):169-74. PubMed ID: 11306517.
    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.
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