RESUMEN
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.
Asunto(s)
Humanos , Masculino , Western Blotting , Técnica del Anticuerpo Fluorescente , Fosfatidilinositol 3-Quinasa/genética , Fosforilación/efectos de los fármacos , Neoplasias de la Próstata/genética , Proteínas Proto-Oncogénicas c-akt/genética , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteínas Recombinantes/genética , Transducción de Señal , Esteril-Sulfatasa/genética , Células Tumorales Cultivadas , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Bacterial aortitis is a rare, but fatal, infectious disease underlying an atherosclerotic aorta or normal aortic wall in an immunocompromised host. The commonly identified organisms responsible for the condition are Salmonella, Staphylococcus and Streptococcus, and on rare occasions, E.coli. We report a case of a 57-year-old man with bacterial aortitis and a splenic abscess caused by E.coli, which was successfully treated by periaortic debridement, prosthetic graft replacement, splenectomy and antibiotic therapy.