Regulation of NR4A nuclear receptor expression by oncogenic BRAF in melanoma cells

Smith, Aaron G., Lim, Wen, Pearen, Michael, Muscat, George E. O. and Sturm, Richard A. (2011) Regulation of NR4A nuclear receptor expression by oncogenic BRAF in melanoma cells. Pigment Cell and Melanoma Research, 24 3: 551-563. doi:10.1111/j.1755-148X.2011.00843.x

Author Smith, Aaron G.
Lim, Wen
Pearen, Michael
Muscat, George E. O.
Sturm, Richard A.
Title Regulation of NR4A nuclear receptor expression by oncogenic BRAF in melanoma cells
Journal name Pigment Cell and Melanoma Research   Check publisher's open access policy
ISSN 1755-1471
Publication date 2011-06-01
Year available 2011
Sub-type Article (original research)
DOI 10.1111/j.1755-148X.2011.00843.x
Volume 24
Issue 3
Start page 551
End page 563
Total pages 13
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell Publishing
Language eng
Abstract 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.
Keyword Melanoma
Nuclear receptor
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 511110
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
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