Present address: Department of Biotechnology, Dalian Medical University, Dalian China.
Increased levels of DUSP6 phosphatase stimulate tumourigenesis in a molecularly distinct melanoma subtype
Article first published online: 12 JAN 2012
© 2011 John Wiley & Sons A/S
Pigment Cell & Melanoma Research
Volume 25, Issue 2, pages 188–199, March 2012
How to Cite
Li, W., Song, L., Ritchie, A.-M. and Melton, D. W. (2012), Increased levels of DUSP6 phosphatase stimulate tumourigenesis in a molecularly distinct melanoma subtype. Pigment Cell & Melanoma Research, 25: 188–199. doi: 10.1111/j.1755-148X.2011.00949.x
- Issue published online: 22 FEB 2012
- Article first published online: 12 JAN 2012
- Accepted manuscript online: 15 DEC 2011 03:33AM EST
- PUBLICATION DATA Received 10 August 2011, revised and accepted for publication 8 December 2011, published online 15 December 2011
- anchorage-independent growth;
- MAPK pathway;
The mitogen-activated protein kinase (MAPK) pathway is important in melanoma. In this pathway, DUSP6 phosphatase negatively controls the activation of extracellular signal-regulated (ERK) kinase. Through comparison of melanoma signalling pathways between immortal mouse melanocytes and their tumourigenic derivatives, retrieved from mouse xenografts, we identified a molecularly distinct subtype of melanoma, characterized by reduced ERK activity and increased DUSP6 expression. Overexpression of DUSP6 enhanced anchorage-independent growth and invasive ability of immortal mouse melanocytes, suggesting that increased DUSP6 expression contributes to melanoma formation in the mouse xenografts. In contrast, reduced tumourigenicity was observed after DUSP6 overexpression in human melanoma cells. A minority of thick human primary melanomas had high DUSP6 expression and the same poor melanoma-specific survival as the majority of thick primaries with low DUSP6 levels. We have demonstrated that DUSP6 is important in melanoma and that it plays a different role in our distinct subtype of mouse melanoma compared with that in classic human melanoma.