Rat strain-specific actions of 17β-estradiol in the mammary gland: Correlation between estrogen-induced lobuloalveolar hyperplasia and susceptibility to estrogen-induced mammary cancers
Open accessAbstract
The genetically related ACI and Copenhagen (COP) rat strains display diametrically opposed susceptibilities to mammary cancer development when treated chronically with 17beta-estradiol (E2). Here, we compare the actions of E2 on cell proliferation and lobuloalveolar development in the mammary glands of female ACI and COP rats. After 12 wk of E2 treatment, the mammary glands of ACI rats exhibited a significantly greater proliferative response to E2, compared with COP rats, as evidenced by quantification of S phase fraction and development of lobuloalveolar hyperplasia. Focal regions of atypical epithelial hyperplasia were observed in ACI, but not COP, rats. These strain differences were not because of differences in circulating E2, progesterone or, prolactin. Two-thirds of the induced mammary cancers in ACI rats exhibited aneuploidy. The E2-induced mammary cancers regressed when hormone treatment was discontinued, indicating that they were estrogen-dependent. Progesterone receptor was expressed by the great majority of epithelial cells within the E2-induced atypical hyperplastic foci and the mammary carcinomas, suggesting a link between these lesions. These data demonstrate a correlation between E2 action in the induction of mammary cell proliferation and atypical epithelial hyperplasia and genetically conferred susceptibility to E2-induced mammary cancers.
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These tumors are generally known to be mostly estrogen-dependent.
“These tumors are generally known to be mostly estrogen-dependent (Harvell et al., 2000).”
From RETRACTED: Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize (2012) · cites this paper as Harvell et al., 2000
These tumors are generally known to be mostly estrogen-dependent.
“These tumors are generally known to be mostly estrogen-dependent [63].”
From Republished study: long-term toxicity of a Roundup herbicide and a Roundup-tolerantgenetically modified maize (2014) · cites this paper as [63]
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References 44 · Cited by 96
- Authors
- Harvell, D. M. E., Strecker, T. E., Tochacek, M., Xie, B., Pennington, K. L., McComb, R. D., Roy, S. K., & Shull, J. D.
- Affiliations
- University of Nebraska Medical Center (US)
- Corresponding author
- Shull, James D.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2000-02-25
- Volume
- 97
- Issue
- 6
- Pages
- 2779-2784
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC16006
- OpenAlex
- W2160046059
- Cited by
- 96
- References
- 44
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 1 · 2019: 5 · 2018: 1 · 2017: 1 · 2015: 1 · 2014: 6 · 2013: 5 · 2012: 5
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Institute for Cancer Research
- National Institutes of Health (P30CA36727)
- National Cancer Institute (R01CA068529, R01CA77876, R01CA077876, R01CA68529, P30CA036727, T32CA009476, P-30CA-36727)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Pathology and Forensic Medicine › Breast Lesions and Carcinomas
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Keywords
- estradiol, mammary gland, ACI rats, Copenhagen rat, strain differences, mammary cell proliferation, atypical epithelial hyperplasia, aneuploidy, progesterone receptor, mammary carcinogenesis
- MeSH terms
- Animals, Disease Susceptibility, Estradiol, Female, Flow Cytometry, Hyperplasia, Hyperprolactinemia, Immunohistochemistry, Mammary Glands, Animal, Pituitary Gland, Progesterone, Rats, Inbred ACI, Receptors, Progesterone, Species Specificity, Time Factors, Mammary Neoplasms, Animal, S Phase, Rats
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