Neonatal ultraviolet radiation exposure is critical for malignant melanoma induction in pigmented TPras transgenic mice
Hacker, Elke, Irwin, Nicole, Muller, H. Konrad, Broome-Powell, Marianne, Kay, Graham, Hayward, Nicholas K., & Walker, Graeme J. (2005) Neonatal ultraviolet radiation exposure is critical for malignant melanoma induction in pigmented TPras transgenic mice. The Journal of Investigative Dermatology, 125(5), pp. 1074-1077.
Malignant melanoma (MM) in humans develops within a complex aetiologic framework of genetic, host, and environmental factors (Goldstein & Tucker, 2001). The strongest environmental risk factor is sun exposure (Sulaimon et al., 2003). In the mouse, wild type animals are resistant to MM development even when exposed to repeated treatments with ultraviolet radiation (UVR) (Gallagher et al., 1984). However chronic UVR treatment regimens have increased MM penetrance by up to 26% in mice carrying various transgenes capable of inducing spontaneous MM development, or melanocytic hyperplasia, e.g. Tyr-SV40Tag (Kelsall & Mintz, 1998; Klein-Szanto et al., 1994), TPras (Broome Powell et al., 1999) and Mt-Hgf/Sf (Noonan et al., 2000) mice. More recently, Noonan et al. (2001) showed that a single neonatal dose of 9 kJ/m2 was far more effective than chronic treatments at inducing MM in the Mt-Hgf/Sf transgenics. Kannan et al. (2003) used the neonatal UVR regimen on mice with melanocyte-specific activation of Hras on a background of either Ink4a or Arf nullizygosity. At 22 weeks, Ink4a -/-:Tyr-Hras and Arf -/-:Tyr-Hras animals developed spontaneous MM, with an incidence of 35% and 53% respectively (Chin et al., 1997). Importantly, neonatal UVR exposure resulted in a marked increase in MM development only in the Arf -/-:Tyr-Hras animals (penetrance rose to 88%) (Kannan et al., 2003), implying that a defect in the p53 pathway may be necessary for UVR-induced MM. Arf -/-:Tyr-Hras tumours were characterized by Cdk6 amplification and Ink4a mutation, genetic lesions that were never observed in non–UVR induced MM. Notably, these secondary mutations indicate that these UVR-induced MM may only arise on an activated Hras background when both the p53 and pRb pathways are compromised.
Citation countsare sourced monthly fromand citation databases.
These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.
Citations counts from theindexing service can be viewed at the linked Google Scholar™ search.
Full-text downloadsdisplays the total number of times this work’s files (e.g., a PDF) have been downloaded from QUT ePrints as well as the number of downloads in the previous 365 days. The count includes downloads for all files if a work has more than one.
|Item Type:||Journal Article|
|Additional Information:||Short title: Neonatal UVR critical for melanoma in TPras mice|
|Keywords:||UVR, Ultraviolet radiation, PI3K, Phosphatidylinositol 3-kinase, MAPK, Mitogen-activated protein kinase, MM, Malignant melanoma, Hras, Mouse melanoma|
|Subjects:||Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > PUBLIC HEALTH AND HEALTH SERVICES (111700) > Public Health and Health Services not elsewhere classified (111799)|
|Divisions:||Current > QUT Faculties and Divisions > Faculty of Health|
Current > Schools > School of Public Health & Social Work
|Copyright Owner:||Copyright 2005 Nature Publishing Group|
|Deposited On:||11 Jun 2009 13:12|
|Last Modified:||29 Feb 2012 23:56|
Repository Staff Only: item control page