Expression of ligand-activated KIT and platelet-derived growth factor receptor beta tyrosine kinase receptors in synovial sarcoma.

Abstract

PURPOSE:

The use of tyrosine kinase receptor inhibitors is increasingly becoming a valuable therapeutic alternative in tumors carrying activated tyrosine kinase receptors. In a previous study, we described a coexpression of KIT and stem cell factor (SCF) mRNA in Synovial sarcomas, (SS) and in a limited number of cases, we demonstrated the presence of an activated receptor. Here, in a wider number of cases, we investigated the expression level and phosphorylation status of two structurally related tyrosine kinase receptors, KIT and platelet-derived growth factor receptor beta (PDGFRbeta), at the light of their role as possible targets of tyrosine kinase receptors inhibitor molecules.

EXPERIMENTAL DESIGN:

Forty-three SS cases were analyzed for KIT and PDGFRbeta expression/activation by immunoprecipitation/Western blotting experiments. The cognate ligands, SCF and PDGFB, were detected by reverse transcription-PCR.

RESULTS:

KIT was observed in 48 and 41% (45% total) whereas PDGFRbeta in 54 and 33% (45% total) of monophasic and biphasic SS cases, respectively. With respect to the fusion transcript type SYTSSX1 and SYTSSX2, KIT was more expressed in SYTSSX1 carrying cases (48 versus 38%), whereas PDGFRbeta resulted more frequently expressed in SYTSSX2 ones (54 versus 37%). When expressed, the receptors were phosphorylated. Their ligands were detected in all of the activated cases.

CONCLUSIONS:

About 70% of the cases express one of the two activated tyrosine kinase receptors with a mutually exclusive expression trend. Coexpression is not frequent and seems to be restricted to monophasic subtype. These data indicate that a consistent fraction of this tumor type could represent a good candidate for kinase inhibitor molecules effective on KIT and PDGFRbeta where their activation is sustained by an autocrine loop.

• Authors: Elena Tamborini, Lorena Bonadiman, Angela Greco, Alessandro Gronchi, Carla Riva, Rossella Bertulli, Paolo G Casali, Marco A Pierotti, Silvana Pilotti
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 10 Issue 3 Pg. 938-43 (Feb 01 2004) ISSN: 1078-0432 [Print] United States
• PMID: 14871970 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ligands
• RNA, Messenger
• Recombinant Fusion Proteins
• Stem Cell Factor
• RNA
• Protein-Tyrosine Kinases
• Proto-Oncogene Proteins c-kit
• Receptor Protein-Tyrosine Kinases
• Receptor, Platelet-Derived Growth Factor beta

Topics

• Blotting, Western
• Cell Line, Transformed
• Cell Line, Tumor
• Humans
• Immunohistochemistry
• Ligands
• Phosphorylation
• Precipitin Tests
• Protein-Tyrosine Kinases (metabolism)
• Proto-Oncogene Proteins c-kit (metabolism)
• RNA (metabolism)
• RNA, Messenger (metabolism)
• Receptor Protein-Tyrosine Kinases (metabolism)
• Receptor, Platelet-Derived Growth Factor beta (biosynthesis)
• Recombinant Fusion Proteins (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sarcoma, Synovial (metabolism, pathology)
• Stem Cell Factor (biosynthesis)