.) The long range goal of the proposed research is to understand the role of PAX3-FKHR in alveolar rhabdomyosarcoma (ARMS), a tumor of fetal skeletal origin that is most common in children. PAX3-FKHR is a product of t(2;13) ARMS-associated chromosomal translocations. This chimeric transcription factor contains the PAX3 DNA binding domain and the (stronger) FKHR transactivation domain. Preliminary studies show that PAX3-FKHR aberantly activates the gene for the platelet derived growth factor alpha receptor (PDGFaR). This is the first example of a cellular target gene that is specifically affected by PAX3-FKHR and not PAX3. The first specific aim is to delineate the PAX3-FKHR response element that flanks the PDGFaR gene.
The second aim i s to map the protein motif(s) in PAX3-FKHR that enables it to activate the PDGFaR gene.
The third aim i s to examine how PDGFaR function contributes to ARMS tumor cell growth. Since PDGF is a potent mitotic growth factor, aberrant expression of its receptor is likely to play a crucial role in cell transformation.
| Hu, Qiande; Yuan, Yewen; Wang, Chiayeng (2013) Structural and functional studies of FKHR-PAX3, a reciprocal fusion gene of the t(2;13) chromosomal translocation in alveolar rhabdomyosarcoma. PLoS One 8:e68065 |
| Zhang, Y; Wang, C (2011) Nephroblastoma overexpressed (NOV/CCN3) gene: a paired-domain-specific PAX3-FKHR transcription target that promotes survival and motility in alveolar rhabdomyosarcoma cells. Oncogene 30:3549-62 |
| Zhang, Youbin; Schwartz, Joel; Wang, Chiayeng (2009) Comparative analysis of paired- and homeodomain-specific roles in PAX3-FKHR oncogenesis. Int J Clin Exp Pathol 2:370-83 |
| Nishijo, Koichi; Chen, Qing-Rong; Zhang, Lei et al. (2009) Credentialing a preclinical mouse model of alveolar rhabdomyosarcoma. Cancer Res 69:2902-11 |
