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Ploidy differences between hormone‐ and chemical carcinogen–induced rat mammary neoplasms: Comparison to invasive human ductal breast cancer *
Author(s) -
Li Jonathan J.,
Papa Dan,
Davis Marilyn F.,
Weroha S. John,
Aldaz C. Marcelo,
ElBayoumy Karam,
Ballenger Jodi,
Tawfik Ossama,
Li Sara Antonia
Publication year - 2002
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/mc.10022
Subject(s) - biology , mammary gland , carcinogen , ploidy , ductal carcinoma , fluorescence in situ hybridization , cancer research , cancer , chromosome , hormone , gene , breast cancer , genetics , endocrinology
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 (E 2 ) in female A‐strain Copenhagen Irish hooded gene rats (ACI) and E 2 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 E 2 ‐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 E 2 ‐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 E 2 ‐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. © 2002 Wiley‐Liss, Inc.