Loss of heterozygosity analysis in primary mammary tumors and lung metastases of MMTV-MTAg and MMTV-neu transgenic mice

Steve R. Ritland, Gerald J. Rowse, Yue Chang, Sandra J Gendler

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Abstract

Loss of heterozygosity (LOH) analysis has been used in many types of human cancer to localize putative tumor suppressor genes important in carcinogenesis. However, this approach has only recently been applied to transgenic mouse tumor models, which offer greater opportunity for detailed molecular genetic analysis of tumor initiation and progression. To explore the possible role of secondary genetic events in transgenic mouse mammary tumor development, we performed microsatellite-based allelotypes on primary mammary adenocarcinomas and lung metastases arising in mice transgenic for the polyomavirus middle T antigen under the control of the mouse mammary tumor virus promoter/enhancer (MMTV-MTAg mice) and on primary mammary adenocarcinomas arising in mice transgenic for the neu proto-oncogene (MMTV- neu mice). We examined a total of 80 microsatellite loci distributed throughout the mouse genome for LOH and observed high rates of specific chromosomal loss but very low rates of background allelic loss in these tumors. For the MMTV-MTAg mice, no individual chromosomes showed rates of LOH significantly above the background rates. For MMTV-neu mice, markers on chromosome 4 showed LOH in 82% of mammary tumors, whereas markers on chromosome 3 showed loss in 29% of tumors. These data suggest that the middle T antigen transgenic mice do not undergo whole chromosome loss or large genomic deletions as common mechanisms of tumor formation and that chromosomes 3 and 4 may contain tumor suppressor gene loci that play important roles in the development of neu-mediated mouse mammary tumors.

Original languageEnglish (US)
Pages (from-to)3520-3525
Number of pages6
JournalCancer Research
Volume57
Issue number16
StatePublished - Aug 15 1997

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Loss of Heterozygosity
Transgenic Mice
Breast Neoplasms
Neoplasm Metastasis
Lung
Neoplasms
Chromosomes, Human, Pair 4
Chromosomes, Human, Pair 3
Tumor Suppressor Genes
Microsatellite Repeats
Breast
Chromosomes
Mouse mammary tumor virus
Polyomavirus Transforming Antigens
Proto-Oncogenes
Viral Tumor Antigens
Tumor Biomarkers
Carcinogens
Molecular Biology
Carcinogenesis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Loss of heterozygosity analysis in primary mammary tumors and lung metastases of MMTV-MTAg and MMTV-neu transgenic mice. / Ritland, Steve R.; Rowse, Gerald J.; Chang, Yue; Gendler, Sandra J.

In: Cancer Research, Vol. 57, No. 16, 15.08.1997, p. 3520-3525.

Research output: Contribution to journalArticle

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