Acceleration of mammary neoplasia in aromatase transgenic mice by 7,12-dimethylbenz[a]anthracene

Nagalakshmi Keshava, Usha Mandava, Nameer Kirma, Rajeshwar Rao Tekmal

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Our studies using the aromatase transgenic mice model have shown that early exposure of mammary epithelium to in situ estrogen as a result of overexpression of aromatase predispose mammary tissue to preneoplastic changes. Here, we hypothesize that the preneoplastic changes induced by mammary estrogen in aromatase transgenic females may be susceptible to environmental carcinogens like 7,12-dimethylbenz[a]anthracene (DMBA), and may result in the acceleration and/or increase in the incidence of breast cancer. Results presented in this study show that tumors appeared in 25% of the mice that were treated with DMBA and all treated transgenic animals had microscopic evidence of neoplastic progression. Control non-transgenic females did not have significant changes even after treatment with DMBA. Consistent with increased neoplastic changes in DMBA-treated aromatase mice, we have seen an increase in the expression of genes involved in cell proliferation and cell cycle. We have also seen changes in the expression of oxidative stress markers and changes in estrogen-mediated growth factors. These studies indicate that more than one event is required for tumor formation, and that early estrogen exposure leading to preneoplastic changes in the mammary epithelial cells increases susceptibility to environmental carcinogens that may result in acceleration and/or an increase in the incidence of breast cancer.

Original languageEnglish (US)
Pages (from-to)125-133
Number of pages9
JournalCancer Letters
Volume167
Issue number2
DOIs
StatePublished - Jun 26 2001
Externally publishedYes

Keywords

  • 7,12-Dimethylbenz[a]anthracene carcinogenesis
  • Aromatase
  • Breast cancer
  • Gene regulation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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