No conflicts of interest were declared.
c-Jun amplification and overexpression are oncogenic in liposarcoma but not always sufficient to inhibit the adipocytic differentiation programme†
Article first published online: 8 APR 2009
Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 218, Issue 3, pages 292–300, July 2009
How to Cite
Snyder, E. L., Sandstrom, D. J., Law, K., Fiore, C., Sicinska, E., Brito, J., Bailey, D., Fletcher, J. A., Loda, M., Rodig, S. J., Dal Cin, P. and Fletcher, C. D. (2009), c-Jun amplification and overexpression are oncogenic in liposarcoma but not always sufficient to inhibit the adipocytic differentiation programme. J. Pathol., 218: 292–300. doi: 10.1002/path.2564
- Issue published online: 5 JUN 2009
- Article first published online: 8 APR 2009
- Accepted manuscript online: 8 APR 2009 12:00AM EST
- Manuscript Accepted: 25 MAR 2009
- Manuscript Received: 1 MAR 2009
- Manuscript Revised: 1 MAR 2009
- Molecular Oncologic Pathology of the Dana Farber Cancer Institute and Brigham and Women's Hospital
Genomic amplification of c-Jun and its upstream kinases have been implicated as a mechanism of progression from well-differentiated to dedifferentiated liposarcoma. To further define the role of c-Jun in liposarcoma progression, we performed immunohistochemistry for c-Jun and its activating kinase ASK1 on a series of liposarcomas (n = 81). We correlated the results with fluorescence in situ hybridization to detect c-Jun amplification. We also derived new cell lines from dedifferentiated liposarcomas with c-Jun amplification. c-Jun protein is expressed in the majority of dedifferentiated liposarcomas (91%) and their well-differentiated components (59%), but only in the minority of pure well-differentiated liposarcomas (27%). When c-Jun is amplified in dedifferentiated liposarcoma, it is interspersed with amplified MDM2 on ring and giant marker chromosomes. MDM2 amplification is one of the earliest events in liposarcoma development, and these results suggest that c-Jun was amplified at a similar time in the evolution of the tumour. In addition, shRNA to c-Jun in c-Jun-amplified liposarcoma cells reduces cell number in vitro and inhibits tumour formation in vivo without an observable effect on the differentiation state of the liposarcoma cells. Thus, c-Jun amplification is oncogenic in liposarcomas but not always sufficient for inhibition of adipocytic differentiation. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.