KMID : 0620920110430110646
|
|
Experimental & Molecular Medicine 2011 Volume.43 No. 11 p.646 ~ p.652
|
|
Induction of steroid sulfatase expression by tumor necrosis factor-¥á through phosphatidylinositol 3-kinase/Akt signaling pathway in PC-3 human prostate cancer cells
|
|
Suh Bo-Young
Jung Jin-Joo Park Na-Hee Seong Cheul-Hun Im Hee-Jung Kwon Yeo-Jung Kim Dong-Hak Chun Young-Jin
|
|
Abstract
|
|
|
Steroid sulfatase (STS) is responsible for the hydrolysis of aryl and alkyl steroid sulfates and has a pivotal role in regulating the formation of biologically active estrogens. STS may be considered a new promising drug target for treating estrogen-mediated carcinogenesis. However, the molecular mechanism of STS expression is not well-known. To investigate whether tumor necrosis factor (TNF)-¥á is able to regulate gene transcription of STS, we studied the effect of TNF-¥á on STS expression in PC-3 human prostate cancer cells. RT-PCR and Western blot analysis showed that TNF-¥á significantly induced the expression of STS mRNA and protein in a concentration- and time-dependent manner. Treatment with TNF-¥á resulted in a strong increase in the phosphorylation of Akt on Ser-473 and when cells were treated with phosphatidylinositol (PI) 3-kinase inhibitors such as LY294002 or wortmannin, or Akt inhibitor (Akt inhibitor IV), induction of STS mRNA expression by TNF-¥á was significantly prevented. Moreover, activation of Akt1 by expressing the constitutively active form of Akt1 increased STS expression whereas dominant-negative Akt suppressed TNF-¥á-mediated STS induction. We also found that TNF-¥á is able to increase STS mRNA expression in other human cancer cells such as LNCaP, MDA-MB-231, and MCF-7 as well as PC-3 cells. Taken together, our results strongly suggest that PI 3-kinase/Akt activation mediates induction of human STS gene expression by TNF-¥á in human cancer cells.
|
|
KEYWORD
|
|
phosphatidylinositol 3-kinase, prostate neoplasms, proto-oncogene proteins c-akt, steryl-sulfatase, tumor necrosis factor-¥á
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|