PMID- 12519121
OWN - NLM
STAT- MEDLINE
DCOM- 20040209
LR  - 20191025
IS  - 0893-5785 (Print)
IS  - 0893-5785 (Linking)
VI  - 16
IP  - 1
DP  - 2003 Feb
TI  - Animal models of melanoma: an HGF/SF transgenic mouse model may facilitate 
      experimental access to UV initiating events.
PG  - 16-25
AB  - Cutaneous malignant melanoma, the most lethal of the skin cancers, known for its 
      intractability to current therapies, continues to increase in incidence, 
      providing a significant public health challenge. There is a consensus that skin 
      cancer is initiated by sunlight exposure. For non-melanoma skin cancer there is 
      substantial evidence that chronic exposure to the ultraviolet B radiation (UVB) 
      (280-320 nm) portion of the sunlight spectrum is responsible. Experimentally, UVB 
      is mutagenic and chronic UVB exposure can cause non-melanoma skin cancer in 
      laboratory animals. Non-melanoma tumors in animals and in humans show 
      characteristic UVB signature lesions in the tumor suppressor p53 and/or in the 
      patched (PTCH) gene. An action spectrum or wavelength dependence for squamous 
      cell carcinoma in the mouse shows a major peak of efficacy in the UVB. For 
      malignant melanoma, however, the situation is unclear and the critical direct 
      target(s) of sunlight in initiating melanoma and even the wavelengths responsible 
      are as yet unidentified. This lack of information is in major part a result of a 
      paucity of animal models for melanoma which recapitulate the role of sunlight in 
      initiating this disease. The epidemiology of melanoma differs significantly from 
      non-melanoma skin cancer. Intense sporadic sunlight exposure in childhood, 
      probably exacerbated by additional adult exposure, is associated with elevated 
      melanoma risk. Melanoma is also a disease of gene-environment interactions with 
      underlying genetic factors playing a significant role. These major differences 
      indicate that extrapolation from information for non-melanoma skin cancer to 
      melanoma is unlikely to be useful. We summarize in this review the experimental 
      information available on the role of UV radiation in melanoma and give an 
      overview of animal melanoma models. A new model derived by neonatal UV 
      irradiation of hepatocyte growth factor/scatter factor (HGF/SF) transgenic mice 
      is described which recapitulates the etiology, the histopathology and molecular 
      pathogenesis of human disease. It is anticipated that the HGF/SF transgenic model 
      will provide a means to access the mechanism(s) by which sunlight initiates this 
      lethal disease and provide an appropriate vehicle for derivation of appropriate 
      therapeutic and preventive strategies.
FAU - Noonan, Frances P
AU  - Noonan FP
AD  - Laboratory of Photobiology and Photoimmunology, Department of Environmental and 
      Occupational Health, School of Public Health and Health Services, The George 
      Washington University School of Medicine, Washington, DC, USA. drmfpn@gwumc.edu
FAU - Dudek, James
AU  - Dudek J
FAU - Merlino, Glenn
AU  - Merlino G
FAU - De Fabo, Edward C
AU  - De Fabo EC
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Denmark
TA  - Pigment Cell Res
JT  - Pigment cell research
JID - 8800247
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Animals
MH  - *Disease Models, Animal
MH  - Hepatocyte Growth Factor/genetics/*metabolism
MH  - Humans
MH  - Melanoma/*metabolism/pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - Ultraviolet Rays/adverse effects
RF  - 134
EDAT- 2003/01/10 04:00
MHDA- 2004/02/11 05:00
CRDT- 2003/01/10 04:00
PHST- 2003/01/10 04:00 [pubmed]
PHST- 2004/02/11 05:00 [medline]
PHST- 2003/01/10 04:00 [entrez]
AID - 014 [pii]
AID - 10.1034/j.1600-0749.2003.00014.x [doi]
PST - ppublish
SO  - Pigment Cell Res. 2003 Feb;16(1):16-25. doi: 10.1034/j.1600-0749.2003.00014.x.