Transforming growth factor-beta downregulates interleukin-2-induced phosphorylation of signal transducer and activator of transcription 5 in human renal cell carcinoma.
OBJECTIVE
We investigated signal transducer and activator of transcription-5 (STAT5) activation status in renal cell carcinoma (RCC) and the role of transforming growth factor-beta (TGF-beta) in the process.


METHODS
Twenty normal and RCC tissues were obtained from radical nephrectomy specimens for the assessment of expressions of phosphorylated STAT5 (p-STAT5) and TGF-beta1 (Western blot) and for localization and assessment of their relationship (immunohistochemical and immunofluorescence stains). By using four RCC cell lines and four primary cultured cells, the effect of TGF-beta1 and/or interleukin-2 (IL-2) on the expressions of p-STAT5 were analyzed.


RESULTS
In RCC samples, expression of p-STAT5 was significantly reduced while expression of TGF-beta was enhanced compared with normal kidney tissues (P < 0.001 and P = 0.003, respectively). P-STAT5 was observed almost exclusively in the nuclei of normal kidney tissues while TGF-beta was identified in the cytoplasm of cells of both tissues reflecting the Western results. In both RCC cell lines and cells from primary cultures, treatment with TGF-beta or antibody did not significantly alter STAT5 activation. However, TGF-beta significantly suppressed IL-2-induced STAT5 activation, whereas anti-TGF-beta antibodies enhanced IL-2-induced STAT5 further.


CONCLUSIONS
STAT5 activation is suppressed in RCC compared with normal renal parenchyma. It may be attributed to the RCC-derived TGF-beta which also interferes with IL-2-induced STAT5 pathway activation.
Song
Cheryn
C
Department of Urology, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Poongnap-dong, Songpa-gu, Seoul, South Korea 138-736.
Jun
Sun-Young
SY
Hong
Jun-Hyuk
JH
Ahn
Hanjong
H
D000328:Adult; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D007376:Interleukin-2 / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000378:metabolism*; D018613:Microscopy, Confocal; D008875:Middle Aged; D010766:Phosphorylation; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007376:Interleukin-2; D050799:STAT5 Transcription Factor; D016212:Transforming Growth Factor beta