title: The hybrid PAX3-FKHR fusion protein of alveolar rhabdomyosarcoma transforms fibroblasts in culture.
abstract: Pediatric alveolar rhabdomyosarcoma is characterized by a chromosomal translocation that fuses parts of the PAX3 and FKHR genes. PAX3 codes for a transcriptional regulator that controls developmental programs, and FKHR codes for a forkhead-winged helix protein, also a likely transcription factor. The PAX3-FKHR fusion product retains the DNA binding domains of the PAX3 protein and the putative activator domain of the FKHR protein. The PAX3-FKHR protein has been shown to function as a transcriptional activator. Using the RCAS retroviral vector, we have introduced the PAX3-FKHR gene into chicken embryo fibroblasts. Expression of the PAX3-FKHR protein in these cells leads to transformation: the cells become enlarged, grow tightly packed and in multiple layers, and acquire the ability for anchorage-independent growth. This cellular transformation in vitro will facilitate studies on the mechanism of PAX3-FKHR-induced oncogenesis.
authors.affiliation: Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: S
authors.initials: S
authors.lastname: Scheidler
authors.forename: W J
authors.initials: WJ
authors.lastname: Fredericks
authors.forename: F J
authors.initials: FJ
authors.lastname: Rauscher
authors.forename: F G
authors.initials: FG
authors.lastname: Barr
authors.forename: P K
authors.initials: PK
authors.lastname: Vogt
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002642:Chick Embryo; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D005347:Fibroblasts; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D006801:Humans; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics*; D014157:Transcription Factors / Q000494:pharmacology*; D014162:Transfection; D014178:Translocation, Genetic
chemical_list: D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse