These authors contributed equally to this work.
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ORIGINAL ARTICLE
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Regulation of NR4A nuclear receptor expression by oncogenic BRAF in melanoma cells
Article first published online: 31 MAR 2011
DOI: 10.1111/j.1755-148X.2011.00843.x
© 2011 John Wiley & Sons A/S
Additional Information
How to Cite
Smith, A. G., Lim, W., Pearen, M., Muscat, G. E. O. and Sturm, R. A. (2011), Regulation of NR4A nuclear receptor expression by oncogenic BRAF in melanoma cells. Pigment Cell & Melanoma Research, 24: 551–563. doi: 10.1111/j.1755-148X.2011.00843.x
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These authors contributed equally to this work.
Publication History
- Issue published online: 16 MAY 2011
- Article first published online: 31 MAR 2011
- Accepted manuscript online: 1 MAR 2011 06:09AM EST
- PUBLICATION DATA Received 18 June 2010, revised and accepted for publication 24 February 2011, published online 1 March 2011
Keywords:
- melanoma;
- nuclear receptor;
- NR4A;
- BRAF;
- beta-catenin
Summary
Activating mutations in the MAPK pathway effectors, NRAS or BRAF, are detected in over 70% of melanomas. Accordingly, the identification of downstream targets of constitutive MAPK signalling in melanoma represents a major goal in understanding the genesis of this disease. We report here the regulation of members of the NR4A family of nuclear receptors by the BRAF-MEK-ERK cascade in melanoma cells. Expression profiling of melanoma cells in which both the NR4A1 and NR4A2 family members have been down-regulated by siRNA revealed alterations in genes associated with proliferation, survival and invasiveness of tumour cells. Notably, the up-regulation of Wnt/β-catenin pathway antagonists, DACT1 and CITED1, following NR4A1/2 ablation suggests a possible link between NR4A and β-catenin activity in melanoma cells. Taken together, these data suggest that dysregulation of NR4A nuclear receptors expression and function by the MAPK pathway may contribute to melanoma tumourigenicity.