Submission Title

Analysis of the Effects of Mithramycin on Ewing’s Sarcoma Cell Lines

Author Information

Mary E. DepnerFollow

Location

Jereld R. Nicholson Library

Subject Area

Biochemistry

Description

Ewing’s Sarcoma is a pediatric bone cancer that affects approximately 3 in 1,000,000 children each year. The prognosis for a Ewing’s patient can be very poor due to the extremely aggressive and metastatic nature of Ewing’s Sarcoma cells. Treatment for patients with this cancer typically includes surgery, radiation, and/or chemotherapy. EWS-Fli1, the chromosomal translocation product responsible for the development of Ewing’s Sarcoma, has been shown to upregulate the transcription of the Aurora kinases, a group of serine kinases. As the drug mithramycin has been reported to inhibit expression of EWS-Fli1, we hypothesized that mithramycin might also affect the expression and activity of the Aurora kinases in Ewing’s Sarcoma cells. Mithramycin was tested in the 1960s to determine if it was an effective chemotherapeutic agent, but it was not adopted as a treatment at that time. Recently, renewed interest has developed in using mithramycin in the treatment of solid tumors such as Ewing’s Sarcoma. We report the effects of mithramycin on Ewing’s Sarcoma cell lines RD-ES-1 and SK-ES-1 grown in cell culture. In this study, we attempted to determine a baseline effect of mithramycin on expression of the Aurora kinases and morphology of cells in culture. After treatment with a range of mithramycin concentrations over a period of time, cells were examined for changes in overall morphology and protein localization. Future studies will examine the effects of mithramycin on the global profile of protein expression and modification using 2-D gel electrophoresis.

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Analysis of the Effects of Mithramycin on Ewing’s Sarcoma Cell Lines

Jereld R. Nicholson Library

Ewing’s Sarcoma is a pediatric bone cancer that affects approximately 3 in 1,000,000 children each year. The prognosis for a Ewing’s patient can be very poor due to the extremely aggressive and metastatic nature of Ewing’s Sarcoma cells. Treatment for patients with this cancer typically includes surgery, radiation, and/or chemotherapy. EWS-Fli1, the chromosomal translocation product responsible for the development of Ewing’s Sarcoma, has been shown to upregulate the transcription of the Aurora kinases, a group of serine kinases. As the drug mithramycin has been reported to inhibit expression of EWS-Fli1, we hypothesized that mithramycin might also affect the expression and activity of the Aurora kinases in Ewing’s Sarcoma cells. Mithramycin was tested in the 1960s to determine if it was an effective chemotherapeutic agent, but it was not adopted as a treatment at that time. Recently, renewed interest has developed in using mithramycin in the treatment of solid tumors such as Ewing’s Sarcoma. We report the effects of mithramycin on Ewing’s Sarcoma cell lines RD-ES-1 and SK-ES-1 grown in cell culture. In this study, we attempted to determine a baseline effect of mithramycin on expression of the Aurora kinases and morphology of cells in culture. After treatment with a range of mithramycin concentrations over a period of time, cells were examined for changes in overall morphology and protein localization. Future studies will examine the effects of mithramycin on the global profile of protein expression and modification using 2-D gel electrophoresis.