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, Hans Peter, Bosenberg, Marcus, & 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), pp. 771-780.

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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.

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30 citations in Scopus
26 citations in Web of Science®
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ID Code: 39154
Item Type: Journal Article
Refereed: Yes
Keywords: Cdk4, Mouse Models, Melanoma, naevi, Arf
DOI: 10.1111/j.1755-148X.2010.00752.x
ISSN: 1755-1471
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > PUBLIC HEALTH AND HEALTH SERVICES (111700)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Current > Schools > School of Public Health & Social Work
Deposited On: 13 Dec 2010 02:00
Last Modified: 29 Feb 2012 14:24

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