Aberrant activation of interleukin-9 receptor and downstream Stat3/5 in primary T-cell lymphomas in vivo in susceptible B6 and resistant C3H mice.
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.


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-9Ra was exceptionally highly expressed and phosphorylated in primary TL. IL-9Ralpha 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.


CONCLUSIONS
Aberrant expression, modification and activation of IL-9Ralpha and Stat proteins contribute to in vivo growth of TL in a manner linking to the genetic susceptibility to TL induction.
Shang
Yi
Y
Department of Biomolecular Science, Faculty of Science, Toho University, Miyama 2-2-1, Funabashi 274-8510, Japan.
Kakinuma
Shizuko
S
Amasaki
Yoshiko
Y
Nishimura
Mayumi
M
Kobayashi
Yoshiro
Y
Shimada
Yoshiya
Y
D000818:Animals; D002455:Cell Division / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D007113:Immunity, Innate; D053612:Janus Kinases / Q000235:genetics; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000473:pathology; D053651:Receptors, Interleukin-9 / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics*; D050799:STAT5 Transcription Factor / Q000235:genetics*; D013045:Species Specificity; D014158:Transcription, Genetic
D053651:Receptors, Interleukin-9; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494087:Stat3 protein, mouse; D019938:Cyclin D1; D053612:Janus Kinases