Transforming growth factor-β downregulates interleukin-2-induced phosphorylation of signal transducer and activator of transcription 5 in human renal cell carcinoma

被引:8
作者
Song, Cheryn [1 ]
Jun, Sun-Young [1 ]
Hong, Jun-Hyuk [1 ]
Ahn, Hanjong [1 ]
机构
[1] Univ Ulsan, Coll Med, Dept Urol, Asan Med Ctr, Seoul 138736, South Korea
关键词
transforming growth factor-beta; renal cell neoplasm; STAT5;
D O I
10.1007/s00432-007-0192-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose 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-beta(1) (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-beta(1) 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.
引用
收藏
页码:487 / 492
页数:6
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