Differential roles of the pRb and Arf/p53 pathways in murine naevus and melanoma genesis

Ferguson, Blake, Muller, H. Konrad, Handoko, Herlina Y., Khosrotehrani, Kiarash, Beermann, Friedrich, Hacker, Elke, Soyer, H. Peter, Bosenberg, Marcus and Walker, Graeme J. (2010) Differential roles of the pRb and Arf/p53 pathways in murine naevus and melanoma genesis. Pigment Cell and Melanoma Research, 23 6: 771-780. doi:10.1111/j.1755-148X.2010.00752.x

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Author Ferguson, Blake
Muller, H. Konrad
Handoko, Herlina Y.
Khosrotehrani, Kiarash
Beermann, Friedrich
Hacker, Elke
Soyer, H. Peter
Bosenberg, Marcus
Walker, Graeme J.
Title Differential roles of the pRb and Arf/p53 pathways in murine naevus and melanoma genesis
Journal name Pigment Cell and Melanoma Research   Check publisher's open access policy
ISSN 1755-1471
Publication date 2010-12
Sub-type Article (original research)
DOI 10.1111/j.1755-148X.2010.00752.x
Volume 23
Issue 6
Start page 771
End page 780
Total pages 10
Place of publication Oxford, United Kingdom
Publisher Blackwell Munksgaard
Collection year 2011
Language eng
Formatted abstract
We report on a systematic analysis of genotype-specific melanocyte (MC) UVR responses in transgenic mouse melanoma models along with tumour penetrance and comparative histopathology. pRb or p53 pathway mutations cooperated with NrasQ61K to transform MCs. We previously reported that MCs migrate from the follicular outer root sheath into the epidermis after neonatal UVR. Here, we found that Arf or p53 loss markedly diminished this response. Despite this, mice carrying these mutations developed melanoma with very early age of onset after neonatal UVR. Cdk4R24C did not affect the MC migration. Instead, independent of UVR exposure, interfollicular dermal MCs were more prevalent in Cdk4R24C mice. Subsequently, in adulthood, these mutants developed dermal MC proliferations reminiscent of superficial congenital naevi. Two types of melanoma were observed in this model. The location and growth pattern of the first was consistent with derivation from the naevi, while the second appeared to be of deep dermal origin. In animals carrying the Arf or p53 defects, no naevi were detected, with all tumours ostensibly skipping the benign precursor stage in progression.
© 2010 John Wiley & Sons A/S.
Keyword Cdk4
Mouse Models
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article first published online: 1 SEP 2010

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2011 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 25 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 29 times in Scopus Article | Citations
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Created: Sun, 07 Nov 2010, 00:03:23 EST