Project Details


DESCRIPTION: (adapted from the investigator's abstract) The incidence of
malignant melanoma is increasing at a rate greater than that of any other
human cancer. The etiologic factors contributing to the development of
malanoma are multiple; genetic factors may be considered to be of primary
importance with secondary contributions from carcinogenic stimuli. Several
oncogenes and tumor suppressor genes have been implicated in melanoma
progression, however, no particular amplification, mutation, or
rearrangement of these genes has been found to contribute to transformation.
To implicate an oncogene in the onset of malanoma development, a gain of
function, most likely through mutation of an existing gene, is required.
Conversely, inactivation of a tumor suppressor gene can be achieved through
a number of different mechanisms, including mutation, deletion, or

Transgenic mice provide model systems that can be used to broaden the
understanding of human diseases. Currently, very few experimental animal
models exist for melanoma formation and all mouse models require a
combination of carcinogen and UV treatments. In contrast, a lone of
transgenic mice was generated in the laboratory that displays a phenotype
similar to melanoma without exposure to any known stimuli. The animals
showed areas of pigmented spots on the ear at 10 to 14 days after birth
followed by appearance of raised pigmented lesions by about 2 to 3 months of
age. The majority of the animals died before one year of age. They propose
a set of experiments to study the host gene(s) which was interrupted by the
insertion of the transgene. This interruption may have activated an "off"
oncogene to the "on" state, thus activating its expression and resulting in
the transformation of cells. Alternatively, their transgene may have
interrupted a tumor suppressor gene, thus leading to unrestricted expansion
of targeted cells. A third possibility is specific interaction(s)
transpired between the transgene and the interrupted host sequences, such
interaction(s) resulted in tumor development.

To distinguish among these possibilities, they propose a set of experiments
to isolate and characterize the gene product of the disrupted host
sequences. Analysis of the DNA sequences from cDNA clones will be done
first to see if the sequences is known or novel. If the DNA sequences are
of a known "oncogene" or "tumor suppressor gene", regulation of its
expression will be examined in the system. If the DNA sequences have not
been described, in vitro biological assays will be done to see if it is a
general or specific "oncogene" or "tumor suppressor gene". Regulation of
expression of this putative gene in normal and tumor cells will be done.
Involvement of this putative gene in human melanoma tumors will be studied.
The long term goal is to use this line of transgenic mice as a model system
for the molecular, and genetic characterization of the development of
Effective start/end date12/8/975/31/04


  • National Cancer Institute
  • National Cancer Institute: $66,433.00
  • National Cancer Institute: $351,432.00
  • National Cancer Institute
  • National Cancer Institute: $192,599.00
  • National Cancer Institute: $38,875.00
  • National Cancer Institute: $246,036.00
  • National Cancer Institute
  • National Cancer Institute: $38,808.00


  • Oncology
  • Cancer Research


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