STAT5 activation is required for interleukin-9-dependent growth and transformation of lymphoid cells.

Demoulin, Jean Baptiste;Uyttenhove, Catherine;Lejeune, D.;Mui, A;Renauld, Jean-Christophe;et.al.
(2000) Cancer research — Vol. 60, n° 14, p. 3971-3977 (2000)

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Abstract
Interleukin-9 (IL-9) is a growth factor for T cells and various hematopoietic and lymphoid tumor cells. IL-9 signaling involves activation of Janus kinase (JAK)1 and JAK3 kinases, and signal transducer and activator of transcription (STAT)1, STAT3 and STAT5. Using a dominant negative form of STAT5 (STAT5delta), we demonstrated that this factor is an important mediator of IL-9-dependent Ba/F3 cell growth. Mutation of the STAT binding site of the IL-9 receptor (tyr116phe) results in an important decrease in STAT activation and inhibition of proliferation in the presence of IL-9. A small number of cells escape this inhibition, and IL-9-dependent cell lines could be derived. The selected cells required activation of STAT5 for growth, which was blocked by STAT5delta expression and enhanced by overexpression of wild-type STAT5. In contrast to parental cells, Ba/F3-Phe116 cells growing in the presence of IL-9 further progress to cytokine-independent tumorigenic clones. These tumorigenic clones exhibited a strong cytokine-independent activation of JAK1 and STAT5, which most likely supports their proliferation. Transfection of a constitutively activated variant of STAT5 promoted the growth of wild-type Ba/F3 cells in the absence of cytokine. Finally, the expression of the proto-oncogene pim-1 was correlated with STAT5 activation and cell growth. Our data suggest that STAT5 is an important mediator of IL-9-driven proliferation and that dysregulation of STAT5 activation favors tumorigenesis of lymphoid cells.
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Demoulin, J. B., Uyttenhove, C., Lejeune, D., Mui, A., Groner, B., & Renauld, J.-C. (2000). STAT5 activation is required for interleukin-9-dependent growth and transformation of lymphoid cells. Cancer research, 60(14), 3971-3977. https://hdl.handle.net/2078.5/57371 (Original work published 2000)