TGF-β INHIBITS CYP17 TRANSCRIPTION IN H295R CELLS ACTING VIA ACTIVIN RECEPTOR-LIKE KINASE 5

被引：5
作者：
Derebecka-Holysz, Natalia [1 ,2 ]
Lehmann, Tomasz P. [1 ]
Holysz, Marcin [1 ]
Trzeciak, Wieslaw H. [1 ]
机构：
[1] Univ Med Sci, Dept Biochem & Mol Biol, PL-60781 Poznan, Poland
[2] Inst Nat Fibres & Med Plants, Poznan, Poland
来源：
ENDOCRINE RESEARCH | 2009年 / 34卷 / 03期
关键词：
H295R Cells; CYP17; Expression; TGF-beta; ALK5; GROWTH-FACTOR; TRANSFORMING GROWTH-FACTOR-BETA-1; ADRENOCORTICAL-CELLS; ADRENAL-CORTEX; EXPRESSION; GENE; STEROIDOGENESIS; TGF-BETA-1; SB-431542; PROMOTER;
D O I：
10.1080/07435800903137050
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Objective. Transforming growth factor beta (TGF-beta) is a potent inhibitor of 17 alpha-hydroxylase/17,20 lyase activity and CYP17 gene expression. We investigated the mechanism how CYP17 is inhibited by TGF-beta in adrenocortical cells. Methods. H295R cells were culture and incubated with TGF-beta, transcription inhibitor (DRB), activin receptor-like kinase 5 ALK5 (T beta RII) inhibitor (SB431542), mitogen activated kinases inhibitors (PD98059 and 5B203580), subsequently using reverse transcription and quantitative PCR (RT-qPCR) we determined CYP17 expression. Rsults. TCF-beta significantly decreased the level a cytochrome P450c17 mRNA and this inhibitory effect of TGF-beta on CYP17 expression required activin receptor-like kinase 5 (ALK5) and on-going transcription. Mitogen activated kinases MEK1 and p38 MAPK are not involved it the inhibitory effect of TCF-beta on CYP17 expression. Conclusion. We concluded that the TGF-beta-dependent decrease of 17 alpha-hydroxylase/17,20 lyase activity in the H295R cells is caused. by inhibition of CYP17 transcription and is mediated by the ALK5 receptor.
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收藏
页码：68 / 79
页数：12
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