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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

Xie, YT; Skytting, B; Nilsson, G; Gasbarri, A; Haslam, K; Bartolazzi, A; Brodin, B; Mandahl, Nils LU and Larsson, O (2002) In Cancer Research 62(13). p.3861-3867
Abstract
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.... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Research
volume
62
issue
13
pages
3861 - 3867
publisher
American Association for Cancer Research Inc.
external identifiers
  • wos:000176579500047
  • pmid:12097301
  • scopus:0036645310
ISSN
1538-7445
language
English
LU publication?
yes
id
f9b83e44-b930-4ad8-975c-7f2e519b01e4 (old id 334582)
alternative location
http://cancerres.aacrjournals.org/cgi/reprint/62/13/3861
date added to LUP
2007-11-09 16:10:52
date last changed
2017-02-12 04:13:12
@article{f9b83e44-b930-4ad8-975c-7f2e519b01e4,
  abstract     = {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.},
  author       = {Xie, YT and Skytting, B and Nilsson, G and Gasbarri, A and Haslam, K and Bartolazzi, A and Brodin, B and Mandahl, Nils and Larsson, O},
  issn         = {1538-7445},
  language     = {eng},
  number       = {13},
  pages        = {3861--3867},
  publisher    = {American Association for Cancer Research Inc.},
  series       = {Cancer Research},
  title        = {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},
  volume       = {62},
  year         = {2002},
}