EWS/ETS Regulates DKK Family Expression in Ewing Family Tumor Cells
Author Information
Author(s): Miyagawa Yoshitaka, Okita Hajime, Itagaki Mitsuko, Toyoda Masashi, Katagiri Yohko U., Fujimoto Junichiro, Hata Jun-ichi, Umezawa Akihiro, Kiyokawa Nobutaka
Primary Institution: National Research Institute for Child Health and Development, Setagaya-ku, Tokyo, Japan
Hypothesis
The EWS/ETS fusion proteins regulate the expression of the Dickkopf family in Ewing family tumor cells.
Conclusion
The study suggests that EWS/ETS regulates DKK2 expression, which may affect the tumorigenicity of Ewing family tumors.
Supporting Evidence
- Increased expression of DKK2 and decreased expression of DKK1 were found in Ewing family tumor cells.
- EWS/ETS fusion proteins enhance DKK2 promoter activity but not DKK1.
- Inducible expression of EWS/ETS resulted in strong induction of DKK2 and inhibition of DKK1 in human mesenchymal progenitor cells.
- Mutually exclusive expression of DKK1 and DKK2 was observed in SK-ES1 cells.
- DKK1 expression inhibited tumor growth in immuno-deficient mice.
Takeaway
This study found that a protein called EWS/ETS changes the levels of two related proteins, DKK1 and DKK2, in a type of cancer called Ewing family tumors, which might help the cancer grow.
Methodology
The study used real-time RT-PCR, luciferase reporter assays, and subcutaneous tumorigenicity assays in immuno-deficient mice to analyze gene expression and tumor growth.
Digital Object Identifier (DOI)
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