Prevention of solely estrogen-induced mammary tumors in female ACI rats by tamoxifen: Evidence for estrogen receptor mediation

S. A. Li, S. J. Weroha, O. Tawfik, J. J. Li

Research output: Contribution to journalReview articlepeer-review

56 Scopus citations


There is increasing evidence that both endogenous and exogenously ingested estrogens play a primary role in sporadic breast cancer causation. To establish further that solely estrogen-induced mammary oncogenesis in female ACI rats is an estrogen receptor (ERα)-driven process, we show for the first time that concomitant treatment with the antiestrogen, tamoxifen citrate (TAMc), completely prevents the induction of 17β-estradiol (E2)-induced mammary gland tumors (MGTs). This finding is also supported by the reduced mammary gland (MG) lobulo-alveolar development and proliferative activity observed in TAMc+E2-treated animals compared with MGs from animals treated with E2 alone. These data also correlated with a marked decrease in the number of MG cells expressing ERα and progesterone receptor (PR) in immunostained MG tissue sections from TAMc+E2-treated animals. Additionally, a marked decline in the level of expression of ERα 47, 56 and 66 kDa forms, and PR-A and PR-B was seen in TAMc+E2-treated MGs, compared with MGs treated solely with E2. Thus, both ERα and PR MG profiles in TAMc+E2-treated rats essentially revert to their respective receptor profiles seen in untreated control and TAMc-alone-treated rats. The presence of 56 and 54 kDa isoforms in chronically E2-treated MGs and in MGTs respectively may contribute to fostering the enhanced E2-dependent growth response of both precursor and frank MGT epithelial cells. These findings are consistent with an ERα/PR-mediated MG cell proliferation, a prerequisite for generating the high frequency of chromosomal instability seen in E2-induced ductal carcinomas in situ and primary MGTs in female ACI rats reported by us previously.

Original languageEnglish (US)
Pages (from-to)297-305
Number of pages9
JournalJournal of Endocrinology
Issue number2
StatePublished - Nov 1 2002

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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