Aberrant Activation of Interleukin-9 Receptor and Downstream Stat3/5 in Primary T-cell Lymphomas In Vivo in Susceptible B6 and Resistant C3H Mice

Abstract

Background: Interleukin (IL)-2 family cytokine-mediated signal transduction plays important roles not only in normal development but also in the malignant transformation of lymphoid cells. However, little is known about the status of receptor activation and downstream signal transduction in primary lymphomas in vivo. Materials and Methods: Primary T-cell lymphomas (TL) of mice were induced by X-ray irradiation. Expression and activation of IL-2 family cytokine receptors and downstream Janus kinase (Jak)-signal transducers and activators of transcription (Stat) pathway were determined. Results: IL-9Rα was exceptionally highly expressed and phosphorylated in primary TL. IL-9Rα proteins in TL were heterogeneous due to different glycosylation. Downstream Stat3 and 5, but not Stat1, were also phosphorylated. There was a clear strain difference between susceptible C57BL/6 and resistant C3H mice in Stat3 and 5 activation and expression of Cyclin D1. Conclusion: Aberrant expression, modification and activation of IL-9Rα and Stat proteins contribute to in vivo growth of TL in a manner linking to the genetic susceptibility to TL induction.