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Mature Muscle Fibers Can Revert to Become Cancerous

he fruit fly Drosophila and genetically engineered them to contain human PAX-FKHR gene complexes. The scientists used the insect because its muscles are easily visible through its outer shell. The genes were linked with another gene that made cells glow green if the PAX-FKHR genes were active.

They examined flies with both the PAX7-FKHR complex and PAX3-FKHR complex. Both gene complexes created fatal conditions similar to alveolar rhabdomyosarcoma. For technical reasons, the researchers then focused on PAX7-FKHR, and saw new cells arising from the fully developed muscle tissue. They also saw tumor cells in the larvae’s blood, central nervous system and other locations, indicating that the cells had broken free and metastasized.

Because human and fly genes are nearly identical, it should be possible to test for other genes involved in the cancer by knocking them out, then seeing if that deletion blocks the creation of the cancer.

“We can test virtually every gene in the fly genome,” Dr. Galindo said.

“There has been little progress toward developing effective therapies for rhabdomyosarcoma, in part because of the lack of animal models for the disease,” said Dr. Eric Olson, chairman of molecular biology at UT Southwestern and the study’s senior author. “This work is important because it provides a simple organism, the fruit fly, as a model for analyzing the genetic causes of rhabdomyosarcoma.”

“Second, it reveals a fascinating biological process in which a human gene for rhabdomyosarcoma causes skeletal muscle fibers to undergo a reverse form of development and generate single cells that spread through the organism,” said Dr. Olson, director of the Nancy B. and Jake L. Hamon Center for Basic Research in Cancer and director of the Nearburg Family Center for Basic Research in Pediatric Oncology.



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