Susceptibility to estrogen-induced mammary cancer segregates as an incompletely dominant phenotype in reciprocal crosses between the ACI and copenhagen rat strains

James D. Shull, Karen L. Pennington, Tanya M. Reindl, Mary C. Snyder, Tracy E. Strecker, Thomas J. Spady, Martin Tochacek, Rodney D. Mccomb

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Estrogens have been inextricably linked to the etiology of breast cancer. We have demonstrated that the female ACI rat exhibits a unique propensity to develop mammary cancers when treated continuously with physiological levels of 17β-estradiol (E2). The E2-induced mammary cancers are estrogen dependent and exhibit genomic instability. In contrast, the genetically related Copenhagen (COP) rat strain is relatively resistant to E2-induced mammary cancers. In this study we evaluated susceptibility to E2-induced mammary cancers in first filial (F1), second filial (F2), and backcross (BC) progeny generated from reciprocal intercrosses between the ACI and COP strains. F1 progeny resembled the parental ACI strain with respect to incidence of E2-induced mammary cancers. However, latency was significantly prolonged in the F1 populations. These data indicate that susceptibility behaves as an incompletely dominant phenotype in these crosses. Analysis of phenotypes exhibited by the F1, F2, and BC populations suggests that mammary cancer susceptibility is modified by one or two genetic loci in the reciprocal intercrosses between the ACI and COP strains. Susceptibility to E2-induced mammary cancers did not correlate with E2-induced pituitary growth in the genetically diverse F2 and BC populations, suggesting that the genetic bases for susceptibility to E2-induced mammary cancers differ from those for E2-induced lactotroph hyperplasia.

Original languageEnglish (US)
Pages (from-to)5124-5130
Number of pages7
JournalEndocrinology
Volume142
Issue number12
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Endocrinology

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