Expression of Ligand-Activated KIT and Platelet-Derived Growth Factor Receptor β Tyrosine Kinase Receptors in Synovial Sarcoma

Elena Tamborini, Lorena Bonadiman, Angela Greco, Alessandro Gronchi, Carla Riva, Rossella Bertulli, Paolo G. Casali, Marco A. Pierotti, Silvana Pilotti

Research output: Contribution to journalArticle

51 Citations (Scopus)

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 β (PDGFRβ), 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 PDGFRβ 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 PDGFRβ 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 PDGFRβ 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 PDGFRβ where their activation is sustained by an autocrine loop.

Original languageEnglish
Pages (from-to)938-943
Number of pages6
JournalClinical Cancer Research
Volume10
Issue number3
DOIs
Publication statusPublished - Feb 1 2004

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Synovial Sarcoma
Platelet-Derived Growth Factor Receptors
Receptor Protein-Tyrosine Kinases
Ligands
Stem Cell Factor
Proto-Oncogene Proteins c-sis
Immunoprecipitation
Reverse Transcription
Neoplasms
Research Design
Phosphotransferases
Western Blotting
Phosphorylation
PDGF receptor tyrosine kinase
Light
Polymerase Chain Reaction
Messenger RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Expression of Ligand-Activated KIT and Platelet-Derived Growth Factor Receptor β Tyrosine Kinase Receptors in Synovial Sarcoma. / Tamborini, Elena; Bonadiman, Lorena; Greco, Angela; Gronchi, Alessandro; Riva, Carla; Bertulli, Rossella; Casali, Paolo G.; Pierotti, Marco A.; Pilotti, Silvana.

In: Clinical Cancer Research, Vol. 10, No. 3, 01.02.2004, p. 938-943.

Research output: Contribution to journalArticle

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title = "Expression of Ligand-Activated KIT and Platelet-Derived Growth Factor Receptor β 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 β (PDGFRβ), 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 PDGFRβ 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 PDGFRβ 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 PDGFRβ 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 PDGFRβ where their activation is sustained by an autocrine loop.",
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T1 - Expression of Ligand-Activated KIT and Platelet-Derived Growth Factor Receptor β Tyrosine Kinase Receptors in Synovial Sarcoma

AU - Tamborini, Elena

AU - Bonadiman, Lorena

AU - Greco, Angela

AU - Gronchi, Alessandro

AU - Riva, Carla

AU - Bertulli, Rossella

AU - Casali, Paolo G.

AU - Pierotti, Marco A.

AU - Pilotti, Silvana

PY - 2004/2/1

Y1 - 2004/2/1

N2 - 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 β (PDGFRβ), 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 PDGFRβ 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 PDGFRβ 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 PDGFRβ 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 PDGFRβ where their activation is sustained by an autocrine loop.

AB - 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 β (PDGFRβ), 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 PDGFRβ 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 PDGFRβ 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 PDGFRβ 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 PDGFRβ where their activation is sustained by an autocrine loop.

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