Chromosomal and genetic alterations of 7,12-dimethylbenz[a]anthracene- induced melanoma from TP-ras transgenic mice

Paul R. Gause, Maria Lluria-Prevatt, W. Nicol Keith, Allan Balmain, Spiros Linardopolous, James A Warneke, Marianne B. Powell

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)78-87
Number of pages10
JournalMolecular Carcinogenesis
Volume20
Issue number1
DOIs
StatePublished - Sep 1997

Fingerprint

Chromosomes, Human, Pair 4
Transgenic Mice
Melanoma
Chromosomes, Human, Pair 6
Skin
Cyclin-Dependent Kinase Inhibitor p16
Chromosome Painting
Cell Line
Chromosomes, Human, Pair 3
Paint
ras Genes
Monophenol Monooxygenase
Melanocytes
Tumor Cell Line
Fluorescence In Situ Hybridization
Transgenes
Codon
Chromosome Aberrations
Genes
Neoplasms

Keywords

  • Fluorescence in situ hybridization
  • Melanoma
  • p16
  • Transgenic mice

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

Chromosomal and genetic alterations of 7,12-dimethylbenz[a]anthracene- induced melanoma from TP-ras transgenic mice. / Gause, Paul R.; Lluria-Prevatt, Maria; Keith, W. Nicol; Balmain, Allan; Linardopolous, Spiros; Warneke, James A; Powell, Marianne B.

In: Molecular Carcinogenesis, Vol. 20, No. 1, 09.1997, p. 78-87.

Research output: Contribution to journalArticle

Gause, Paul R. ; Lluria-Prevatt, Maria ; Keith, W. Nicol ; Balmain, Allan ; Linardopolous, Spiros ; Warneke, James A ; Powell, Marianne B. / Chromosomal and genetic alterations of 7,12-dimethylbenz[a]anthracene- induced melanoma from TP-ras transgenic mice. In: Molecular Carcinogenesis. 1997 ; Vol. 20, No. 1. pp. 78-87.
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