SYT-SSX is critical for cyclin D1 expression in synovial sarcoma cells: A gain of function of the t(X;18)(p11.2;q11.2) translocation
Författare
Summary, in English
The SYT-SSX fusion gene has been implicated in the malignant tumor cell growth of synovial sarcoma, but the underlying molecular mechanisms are still poorly understood. Here we demonstrate that SYT-SSX is critical for the protein level of cyclin D1 in synovial sarcoma cells. Antisense oligonucleotides to SYT-SSX mRNA rapidly and drastically decreased cyclin D1 and subsequently inhibited cell growth. This effect is specific for SYT-SSX, without involving the wild-type genes SYT or SSX. The decrease in cyclin D1 expression, which occurred shortly after inhibition of SYT-SSX expression, was found to be primarily dependent on an increased degradation of the cyclin D1 protein, as assessed by pulse-chase experiments using [S-35]methionine. Furthermore, transfection of mouse fibroblasts with SYT-SSX cDNA increased the stability of cyclin D1. Because treatment with a proteasome inhibitor restored cyclin D1 expression, it seems like SYT-SSX interferes with ubiquitin-dependent degradation of cyclin D1. However, SYT-SSX-regulated cyclin D1 expression was proven to be independent of the glycogen synthetase kinase-3beta pathway. Taken together, our study provides evidence that SYT-SSX stabilizes cyclin D1 and is critical for cyclin D1 expression in synovial sarcoma cells. SYT-SSX-dependent expression of cyclin D1 may be an important mechanism in the development and progression of synovial sarcoma and also raises the possibility for targeted therapy.
Avdelning/ar
Publiceringsår
2002
Språk
Engelska
Sidor
3861-3867
Publikation/Tidskrift/Serie
Cancer Research
Volym
62
Issue
13
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
American Association for Cancer Research Inc.
Ämne
- Medical Genetics
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1538-7445