In conclusion, these studies reveal that PAX3, PAX7 and their fusions with FKHR are each expressed in RMS tumors as a consistent mixture of functionally distinct isoforms.
A single tissue microarray containing 71 paraffin-embedded pediatric RMSs was immunostained with antibodies against p53, bcl-2, Ki-67, CD44, myogenin, and MyoD1.
This prompted us to explore the effect of expressing PAX3-FKHR in more relevant cells, specifically primary human skeletal muscle cells because these cells can be converted to a tumorigenic state that mimics rhabdomyosarcoma.
In conclusion, these studies reveal that PAX3, PAX7 and their fusions with FKHR are each expressed in RMS tumors as a consistent mixture of functionally distinct isoforms.
This report describes expression of 11 different mdm2 splice variants in pediatric rhabdomyosarcoma (RMS) cell lines and tumors at a frequency of 75% and 82%, respectively.
This prompted us to explore the effect of expressing PAX3-FKHR in more relevant cells, specifically primary human skeletal muscle cells because these cells can be converted to a tumorigenic state that mimics rhabdomyosarcoma.
Sequential recruitment of PCAF and BRG1 contributes to myogenin activation in 12-O-tetradecanoylphorbol-13-acetate-induced early differentiation of rhabdomyosarcoma-derived cells.
In conclusion, these studies reveal that PAX3, PAX7 and their fusions with FKHR are each expressed in RMS tumors as a consistent mixture of functionally distinct isoforms.
Expression analysis of additional genes, AKT1, NOG and its antagonist BMP4, which interact downstream to FGFR1, demonstrated expression differences between primary RMS tumors and normal skeletal muscles.
Small molecule or blocking antibody-mediated inhibition of CXCR4 or SDF1alpha suppressed RMS cell migration towards BMS-CM, confirming the activity of this axis.
The identification of ezrin and Six-1 as critical regulators of metastasis in RMS provides new mechanistic and therapeutic insights into this pediatric cancer.