The hybrid PAX3-FKHR fusion protein of alveolar rhabdomyosarcoma transforms fibroblasts in culture

Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9805-9. doi: 10.1073/pnas.93.18.9805.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern
  • Cell Transformation, Neoplastic*
  • Cells, Cultured
  • Chick Embryo
  • DNA-Binding Proteins / pharmacology*
  • Fibroblasts
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Humans
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors
  • Rhabdomyosarcoma, Alveolar / genetics*
  • Transcription Factors / pharmacology*
  • Transfection
  • Translocation, Genetic

Substances

  • DNA-Binding Proteins
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • PAX3 Transcription Factor
  • PAX3 protein, human
  • Paired Box Transcription Factors
  • Transcription Factors
  • Pax3 protein, mouse