Ploidy differences between hormone- and chemical carcinogen-induced rat mammary neoplasms

Comparison to invasive human ductal breast cancer

Jonathan J. Li, Dan Papa, Marilyn F. Davis, Saravut (John) Weroha, C. Marcelo Aldaz, Karam El-Bayoumy, Jodi Ballenger, Ossama Tawfik, Sara Antonia Li

Research output: Contribution to journalArticle

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Abstract

To ascertain differences between solely hormone- and chemical carcinogen-induced murine mammary gland tumors (MGTs), a direct comparison of their ploidy status was assessed. Nuclear image cytometry (NIC) was used to evaluate ploidy in ductal carcinoma in situ (DCIS) and MGTs induced solely by 17β-estradiol (E2) in female A-strain Copenhagen Irish hooded gene rats (ACI) and E2 plus testosterone propionate in male Noble rats. These results were compared to ploidy data from primary MGTs induced by two synthetic carcinogens, 7,12-dimethylbenz[a]antracene and nitrosomethylurea in female Brown Lewis Norway rats and an environmental carcinogen, 6-nitrochrysene, in female Sprague-Dawley rats. Both DCIS and primary MGTs induced solely by hormones were highly aneuploid (>84%), whereas MGTs induced by either synthetic or environmental carcinogens were primarily diploid (>85%). Examination of 76 metaphase plates obtained from eight individual E2-induced ACI female rat MGTs revealed the following consistent chromosome alterations: gains in chromosomes 7, 11, 12, 13, 19, and 20 and loss of chromosome 12. On Southern blot analysis, six of nine ACI female rat primary E2-induced MGTs (66%) exhibited amplified copy numbers (range: 3.4-6.9 copies) of the c-myc gene. Fluorescence in situ hybridization (FISH) analysis of these MGTs revealed specific fluorescent hybridization signals for c-myc (7q33) on all three homologs of a trisomy in chromosome 7. NIC analysis of 140 successive nonfamilial sporadic invasive human ductal breast cancers (BCs) showed an aneuploid frequency of 61%, while 31 DCISs revealed a 71% aneuploid frequency. These results clearly demonstrate that the female ACI rat E2-induced MGTs more closely resemble invasive human DCIS and ductal BC in two pertinent aspects: they are highly aneuploid compared with chemical carcinogen-induced MGTs and exhibit a high frequency of c-myc amplification.

Original languageEnglish (US)
Pages (from-to)56-65
Number of pages10
JournalMolecular Carcinogenesis
Volume33
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Animal Mammary Neoplasms
Ploidies
Carcinogens
Human Mammary Glands
Hormones
Breast Neoplasms
Inbred ACI Rats
Carcinoma, Intraductal, Noninfiltrating
Aneuploidy
Image Cytometry
Environmental Carcinogens
Chromosomes, Human, Pair 7
Carcinoma, Ductal, Breast
Testosterone Propionate
Methylnitrosourea
Chromosomes, Human, Pair 12
Chromosomes, Human, Pair 11
myc Genes
Trisomy
Metaphase

Keywords

  • c-myc
  • Estrogens
  • Genomic instability
  • Mammary tumors
  • Ploidy

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

Ploidy differences between hormone- and chemical carcinogen-induced rat mammary neoplasms : Comparison to invasive human ductal breast cancer. / Li, Jonathan J.; Papa, Dan; Davis, Marilyn F.; Weroha, Saravut (John); Aldaz, C. Marcelo; El-Bayoumy, Karam; Ballenger, Jodi; Tawfik, Ossama; Li, Sara Antonia.

In: Molecular Carcinogenesis, Vol. 33, No. 1, 2002, p. 56-65.

Research output: Contribution to journalArticle

Li, Jonathan J. ; Papa, Dan ; Davis, Marilyn F. ; Weroha, Saravut (John) ; Aldaz, C. Marcelo ; El-Bayoumy, Karam ; Ballenger, Jodi ; Tawfik, Ossama ; Li, Sara Antonia. / Ploidy differences between hormone- and chemical carcinogen-induced rat mammary neoplasms : Comparison to invasive human ductal breast cancer. In: Molecular Carcinogenesis. 2002 ; Vol. 33, No. 1. pp. 56-65.
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