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Chromosomal and genetic alterations of 7,12‐ Dimethylbenz[ a ]anthracene–induced melanoma from TP‐ras transgenic mice
Author(s) -
Gause Paul R.,
LluriaPrevatt Maria,
Keith W. Nicol,
Balmain Allan,
Linardopolous Spiros,
Warneke James,
Powell Marianne B.
Publication year - 1997
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199709)20:1<78::aid-mc9>3.0.co;2-e
Subject(s) - biology , genetically modified mouse , chromosomal translocation , microbiology and biotechnology , fluorescence in situ hybridization , transgene , cancer research , melanoma , yeast artificial chromosome , melanocyte , gene , chromosome , genetics , gene mapping
The TP‐ras transgenic mouse line expresses an activated human T24 Ha‐ ras gene with a mutation in codon 12, regulated by a mouse tyrosinase promoter. The transgene is expressed in melanocytes of the skin, eyes, and brain. The mice develop cutaneous melanoma when treated with 7,12‐dimethylbenz[ a ]anthracene. Cell lines have been generated from the cutaneous tumors and metastatic lesions. By using fluorescence in situ hybridization with mouse whole chromosome paints, the cell lines were characterized for chromosomal abnormalities. Key findings in the tumor cells included translocations of chromosome 4 and alterations in chromosome 6. One tumor cell line contained a double translocation involving chromosomes 3 and 6. To extend the results of the chromosome 4 painting, Southern analysis of the p15 INK4B , p16 INK4A , and p19 INK4D genes was performed. Our data indicated that there were homozygous and partial allelic deletions and polymorphisms in the region of chromosome 4 containing these genes, resulting in the absence or reduced expression of the p16 product. These findings are similar to those reported for human melanoma, and the TP‐ras transgenic mouse may therefore be a valuable model for studying novel strategies for melanoma prevention and treatment. Mol. Carcinog. 20:78–87, 1997. © 1997 Wiley‐Liss, Inc.