The cooperative transforming effects of PAX3-FKHR and IGF-II on mouse myoblasts.

Abstract

Alveolar rhabdomyosarcoma (ARMS) cells express high levels of PAX3-FKHR and IGF-II. In this study, we have investigated the effects of PAX3-FKHR and IGF-II on the expression of muscle regulatory factors (myf5, MyoD and myogenin), and platelet derived growth factor-B (PDGF-B) and vascular endothelial growth factor (VEGF) in mouse C2C12 myoblasts in vitro. PAX3-FKHR induced cell cycling of C2C12 cells and promoted proliferation whilst blocking myogenesis. IGF-II inhibited their differentiation without influencing proliferation. Western blotting showed that PAX3-FKHR and IGF-II blocked the expression of myogenin and MyoD respectively. Since MyoD affects early myogenesis and myogenin controls terminal differentiation, a combination of PAX3-FKHR and IGF-II synergistically blocks myogenesis at several different stages in differentiation. We have also shown that the major survival and angiogenic cytokines, PDGF-B and VEGF, were induced by IGF-II and PAX3-FKHR respectively. A combination of PAX3-FKHR and IGF-II could synergistically up regulate the expression of PDGF-B and VEGF and stabilize their high expression levels. Our results suggest that high expression of PAX3-FKHR and IGF-II in ARMS synergistically play a key role in oncogenesis and tumour progression of ARMS.

• Authors: W Wang, M Slevin, S Kumar, P Kumar
• Journal: International journal of oncology (Int J Oncol) Vol. 27 Issue 4 Pg. 1087-96 (Oct 2005) ISSN: 1019-6439 [Print] Greece
• PMID: 16142327 (Publication Type: Journal Article)

Chemical References

• Forkhead Box Protein O1
• Forkhead Transcription Factors
• Foxo1 protein, mouse
• PAX3 Transcription Factor
• Paired Box Transcription Factors
• Proto-Oncogene Proteins c-sis
• Vascular Endothelial Growth Factor A
• Pax3 protein, mouse
• Insulin-Like Growth Factor II

Topics

• Animals
• Apoptosis
• Blotting, Western
• Cell Differentiation
• Cell Line
• Cell Proliferation
• Cell Transformation, Neoplastic
• Cells, Cultured
• Disease Progression
• Flow Cytometry
• Forkhead Box Protein O1
• Forkhead Transcription Factors (physiology)
• Gene Expression Regulation, Neoplastic
• Insulin-Like Growth Factor II (physiology)
• Mice
• Mitosis
• PAX3 Transcription Factor
• Paired Box Transcription Factors (physiology)
• Proto-Oncogene Proteins c-sis (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Rhabdomyosarcoma, Alveolar (metabolism, pathology)
• Time Factors
• Transfection
• Up-Regulation
• Vascular Endothelial Growth Factor A (metabolism)