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

• Published in: Experimental & molecular medicine 2011, 43(11), , pp.646-652
• Main Authors: Suh, Bo-Young, Jung, Jin-Joo, Park, Nahee, Seong, Cheul-Hun, Im, Hee-Jung, Kwon, Yeojung, Kim, Donghak, Chun, Young-Jin
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Blotting, Western; Fluorescent Antibody Technique; Humans; Male; Medical Biochemistry; Molecular Medicine; Original; Phosphatidylinositol 3-Kinase - genetics; Phosphatidylinositol 3-Kinase - metabolism; Phosphorylation - drug effects; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Real-Time Polymerase Chain Reaction; Recombinant Proteins - genetics; Recombinant Proteins - isolation & purification; Recombinant Proteins - metabolism; RNA, Messenger - genetics; Signal Transduction; Stem Cells; Steryl-Sulfatase - genetics; Steryl-Sulfatase - metabolism; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - pharmacology; 생화학
• ISSN: 1226-3613; 2092-6413
• DOI: 10.3858/emm.2011.43.11.073

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.