Induction of steroid sulfatase expression by tumor necrosis factor-alpha through phosphatidylinositol 3-kinase/Akt signaling pathway in PC-3 human prostate cancer cells.
10.3858/emm.2011.43.11.073
- Author:
Bo Young SUH
1
;
Jin Joo JUNG
;
Nahee PARK
;
Cheul Hun SEONG
;
Hee Jung IM
;
Yeojung KWON
;
Donghak KIM
;
Young Jin CHUN
Author Information
1. College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea. yjchun@cau.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
phosphatidylinositol 3-kinase;
prostate neoplasms;
proto-oncogene proteins c-akt;
steryl-sulfatase;
tumor necrosis factor-alpha
- MeSH:
Blotting, Western;
Fluorescent Antibody Technique;
Humans;
Male;
Phosphatidylinositol 3-Kinase/genetics/*metabolism;
Phosphorylation/drug effects;
Prostatic Neoplasms/genetics/*metabolism;
Proto-Oncogene Proteins c-akt/genetics/*metabolism;
RNA, Messenger/genetics;
Real-Time Polymerase Chain Reaction;
Recombinant Proteins/genetics/isolation & purification/metabolism;
Signal Transduction;
Steryl-Sulfatase/genetics/*metabolism;
Tumor Cells, Cultured;
Tumor Necrosis Factor-alpha/*pharmacology
- From:Experimental & Molecular Medicine
2011;43(11):646-652
- CountryRepublic of Korea
- Language:English
-
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)-alpha is able to regulate gene transcription of STS, we studied the effect of TNF-alpha on STS expression in PC-3 human prostate cancer cells. RT-PCR and Western blot analysis showed that TNF-alpha significantly induced the expression of STS mRNA and protein in a concentration- and time-dependent manner. Treatment with TNF-alpha 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-alpha was significantly prevented. Moreover, activation of Akt1 by expressing the constitutively active form of Akt1 increased STS expression whereas dominant-negative Akt suppressed TNF-alpha-mediated STS induction. We also found that TNF-alpha 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-alpha in human cancer cells.
