%0 Journal Article
%T Regulation of interferon pathway in 2-methoxyestradiol-treated osteosarcoma cells
%A Fritz Wimbauer
%A Caihong Yang
%A Kristen L Shogren
%A Minzhi Zhang
%A Ribu Goyal
%A Scott M Riester
%A Michael J Yaszemski
%A Avudaiappan Maran
%J BMC Cancer
%D 2012
%I BioMed Central
%R 10.1186/1471-2407-12-93
%X 2-ME effects on IFN mRNA levels were determined by Real time PCR analysis. Transient transfections followed by reporter assays were used for investigating 2-ME effects on IFN-pathway. Western blot analyses were used to measure protein and phosphorylation levels of IFN-regulated eukaryotic initiation factor-2 alpha (eIF-2¦Á).2-ME regulates IFN and IFN-mediated effects in osteosarcoma cells. 2 -ME induces IFN gene activity and expression in osteosarcoma cells. 2-ME treatment induced IFN-stimulated response element (ISRE) sequence-dependent transcription and gamma-activated sequence (GAS)-dependent transcription in several osteosarcoma cells. Whereas, 2-ME did not affect IFN gene and IFN pathways in normal primary human osteoblasts (HOB). 2-ME treatment increased the phosphorylation of eIF-2¦Á in osteosarcoma cells. Furthermore, analysis of osteosarcoma tissues shows that the levels of phosphorylated form of eIF-2¦Á are decreased in tumor compared to normal controls.2-ME treatment triggers the induction and activity of IFN and IFN pathway genes in 2-ME-sensitive osteosarcoma tumor cells but not in 2-ME-resistant normal osteoblasts. In addition, IFN-signaling is inhibited in osteosarcoma patients. Thus, IFN pathways play a role in osteosarcoma and in 2-ME-mediated anti-proliferative effects, and therefore targeted induction of IFN signaling could lead to effective treatment strategies in the control of osteosarcoma.
%K 2-Methoxyestradiol
%K osteosarcoma
%K Interferon
%K ISRE
%K GAS
%U http://www.biomedcentral.com/1471-2407/12/93/abstract