Regulation of target genes of PAX3-FOXO1 in alveolar rhabdomyosarcoma.
Copyright policy )Regulation of target genes of PAX3-FOXO1 in alveolar rhabdomyosarcoma.
The majority of alveolar rhabdomyosarcoma (ARMS) are distinguished through the paired box 3-forkhead box protein O1 (PAX3-FOXO1) fusion oncoprotein, being generated by a 2;13 chromosomal translocation. This fusion-positive ARMS is the most clinically difficult type of rhabdomyosarcoma. The present study characterized four genes [gremlin 1 (GREM1), death-associated protein kinase-1 (DAPK1), myogenic differentiation-1 (MYOD1), and hairy/enhancer-of-split related with YRPW motif-1 (HEY1)] as targets of PAX3-FOXO1.The expression of the four genes, PAX3-FOXO1, and v-myc myelocytomatosis viral-related oncogene, neuroblastoma-derived (avian) (MYCN) was determined in various ARMS cell models and primary tumors. The roles of PAX3-FOXO1 and MYCN expression were examined.Pulse-chase and cycloheximide experiments suggest that GREM1, DAPK1, and MYOD1 are directly regulated by PAX3-FOXO1. PAX3-FOXO1 appears to indirectly down-regulate HEY1 by up-regulating MYCN. Data reveal that the growth-suppressive activity of high PAX3-FOXO1 expression is closely-associated with up-regulation of the GREM1 and DAPK1 tumor-suppressor genes.This study characterized four downstream targets of PAX3-FOXO1 that contribute to the biological activities of growth suppression and myogenic differentiation.
- University of Pennsylvania United States
Basic Helix-Loop-Helix Proteins, Oncogene Proteins, N-Myc Proto-Oncogene Protein, Forkhead Box Protein O1, Blotting, Western, Nuclear Proteins, Cell Cycle Proteins, Cell Differentiation, Forkhead Transcription Factors, Gene Expression Regulation, Neoplastic, Death-Associated Protein Kinases, Mice, Calcium-Calmodulin-Dependent Protein Kinases, NIH 3T3 Cells, Animals, Humans, Intercellular Signaling Peptides and Proteins, Apoptosis Regulatory Proteins, Cell Proliferation, MyoD Protein
Basic Helix-Loop-Helix Proteins, Oncogene Proteins, N-Myc Proto-Oncogene Protein, Forkhead Box Protein O1, Blotting, Western, Nuclear Proteins, Cell Cycle Proteins, Cell Differentiation, Forkhead Transcription Factors, Gene Expression Regulation, Neoplastic, Death-Associated Protein Kinases, Mice, Calcium-Calmodulin-Dependent Protein Kinases, NIH 3T3 Cells, Animals, Humans, Intercellular Signaling Peptides and Proteins, Apoptosis Regulatory Proteins, Cell Proliferation, MyoD Protein
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