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

Citation

Ferguson, B and Muller, HK and Handoko, HY and Khosrotehrani, K and Beermann, F and Hacker, E and Soyer, HP and Beerman, F and Hacker, E and Soyer, HP and Bosenberg, M and Walker, GJ, Differential roles of the pRb and Arf/p53 pathways in murine naevus and melanoma genesis, Pigment cell & melanoma research, 23, (6) pp. 771-80. ISSN 1755-1471 (2015) [Refereed Article]

DOI: doi:10.1111/j.1755-148X.2010.00752.x

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 Nras(Q61K) 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. Cdk4(R24C) did not affect the MC migration. Instead, independent of UVR exposure, interfollicular dermal MCs were more prevalent in Cdk4(R24C) 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.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Tumour Immunology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Muller, HK (Professor Konrad Muller)
ID Code:106079
Year Published:2015 (online first 2011)
Web of Science® Times Cited:28
Deposited By:Medicine (Discipline)
Deposited On:2016-01-28
Last Modified:2016-01-28
Downloads:0

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