Differential roles of SS18-SSX fusion gene and insulin-like growth factor-1 receptor in synovial sarcoma cell growth.
Recently we demonstrated that the synovial sarcoma specific fusion gene SS18-SSX is crucial for cyclin D1 expression and is linked to cell proliferation. In this report we explore the role of SS18-SSX and IGF-1R for their potential functions in cellular proliferation and survival in cultured synovial sarcoma cells. We found that targeting of SS18-SSX mRNA by antisense oligonucleotide treatment drastically and rapidly decreased cell proliferation but caused only a slight increase of apoptosis. The synovial sarcoma cells were confirmed to express IGF-1R, and treatment with an IGF-1R inhibitor resulted in substantially reduced cell viability by inducing apoptosis in these cells. Conversely, inhibition of the IGF-1R resulted only in a slight to moderate decrease in DNA synthesis. In conclusion, SS18-SSX and IGF-1R seem to play important but different roles in maintaining malignant growth of synovial sarcoma cells. Whereas SS18-SSX maintains cyclin D1 and cell proliferation, IGF-1R protects from apoptosis.
Törnkvist
Maria
M
Department of Oncology and Pathology, Karolinska Institute, CCK, R8:04, S-17176 Stockholm, Sweden.
Natalishvili
Natalia
N
Xie
Yuntao
Y
Girnita
Ada
A
D'Arcy
Pádraig
P
Brodin
Bertha
B
Axelson
Magnus
M
Girnita
Leonard
L
D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D013584:Sarcoma, Synovial / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction
D015514:Oncogene Proteins, Fusion; C116512:SYT-SSX fusion protein; D017526:Receptor, IGF Type 1