Induction of steroid sulfatase expression by tumor necrosis factor-α through phosphatidylinositol 3-kinase/Akt signaling pathway in PC-3 human prostate cancer cells.

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)-α is able to regulate gene transcription of STS, we studied the effect of TNF-α on STS expression in PC-3 human prostate cancer cells. RT-PCR and Western blot analysis showed that TNF-α significantly induced the expression of STS mRNA and protein in a concentration- and time-dependent manner. Treatment with TNF-α 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-α was significantly prevented. Moreover, activation of Akt1 by expressing the constitutively active form of Akt1 increased STS expression whereas dominant-negative Akt suppressed TNF-α-mediated STS induction. We also found that TNF-α 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-α in human cancer cells.

• Authors: Bo Young Suh, Jin Joo Jung, Nahee Park, Cheul Hun Seong, Hee Jung Im, Yeojung Kwon, Donghak Kim, Young Jin Chun
• Journal: Experimental & molecular medicine (Exp Mol Med) Vol. 43 Issue 11 Pg. 646-52 (Nov 30 2011) ISSN: 2092-6413 [Electronic] United States
• PMID: 21904110 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Recombinant Proteins
• Tumor Necrosis Factor-alpha
• Phosphatidylinositol 3-Kinase
• Proto-Oncogene Proteins c-akt
• Steryl-Sulfatase

Topics

• 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)