Cited by 196Estrogen and related hormone effectsBreast Cancer Treatment StudiesEffects and risks of endocrine disrupting chemicals

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Effects of estrogen on breast cancer development: Role of estrogen receptor independent mechanisms

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Yue, Wei, Wang, Ji‐Ping, Li, Yuebai, Fan, Ping, Liu, Guijian, Zhang, Nan, Conaway, Mark, Wang, Hongkun, Korach, Kenneth S., Bocchinfuso, Wayne, Santen, Richard·2010·International Journal of Cancer

DOI 10.1002/ijc.25207PMC PMC4775086

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Abstract

Development of breast cancer involves genetic factors as well as lifetime exposure to estrogen. The precise molecular mechanisms whereby estrogens influence breast tumor formation are poorly understood. While estrogen receptor α (ERα) is certainly involved, nonreceptor mediated effects of estradiol (E2) may also play an important role in facilitating breast tumor development. A “reductionist” strategy allowed us to examine the role of ERα independent effects of E2 on mammary tumor development in ERα knockout (ERKO) mice bearing the Wnt‐1 oncogene. Exogenous E2 “clamped” at early follicular and midluteal phase levels (i.e., 80 and 240 pg/ml) accelerated tumor formation in a dose‐related fashion in ERKO/Wnt‐1 animals (p = 0.0002). Reduction of endogenous E2 by oophorectomy (p < 0.001) or an aromatase inhibitor (AI) (p = 0.055) in intact ERKO/Wnt‐1 animals delayed tumorigenesis as further evidence for an ER‐independent effect. The effects of residual ERα or β were not involved since enhancement of tumor formation could not be blocked by the antiestrogen fulvestrant. 17α‐OH‐E2, a metabolizable but ER‐impeded analogue of E2 stimulated tumor development without measurable uterine stimulatory effects. Taken together, our results suggest that ER‐independent actions of E2 can influence breast tumor development in concert with ER dependent effects. These observations suggest 1 mechanism whereby AIs, which block E2 synthesis, would be more effective for breast cancer prevention than use of antiestrogens, which only block ER‐mediated effects.

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Intra-tumoural estrogen sulfotransferase (hSULT1E1) regulations in human breast cancer tissues are influenced by cellular redox-modifications through antioxidants and Nrf-2/NFκβ interplay.Preprint
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“It initiates mutations that occur as a function of errors during DNA replication [26].”
Background
Menopause
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Authors: Yue, W., Wang, J., Li, Y., Fan, P., Liu, G., Zhang, N., Conaway, M., Wang, H., Korach, K. S., Bocchinfuso, W., & Santen, R.
Affiliations: University of Virginia Health System (US)
National Institutes of Health (US)
Corresponding author: Yue, Wei
ORCID: Yue, Wei
Li, Yuebai
Fan, Ping
Zhang, Nan
Conaway, Mark
Wang, Hongkun
Korach, Kenneth S.
Santen, Richard
Venue: International Journal of Cancer
Publisher: Wiley
Published: 2010-08-20
Volume: 127
Issue: 8
Pages: 1748-1757
ISSN: 0020-7136 (ISSN-L)
1097-0215
DOI: 10.1002/ijc.25207
PMC: PMC4775086
OpenAlex: W2035185970
Cited by: 196
References: 73
Citations by year: 2026: 2 · 2025: 26 · 2024: 16 · 2023: 30 · 2022: 19 · 2021: 23 · 2020: 21 · 2019: 10 · 2018: 10 · 2017: 7 · 2016: 3 · 2015: 5 · 2014: 6 · 2013: 7 · 2012: 9
FWCI: 3.24
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: International Journal of Cancer (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute of Environmental Health Sciences (Z01ES070065)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
Keywords: breast cancer, estrogen receptor alpha, estrogen receptor beta, estradiol, ER knockout mice, aromatase inhibitors, oophorectomy, fulvestrant, breast cancer prevention, antiestrogens
MeSH terms: Fulvestrant, Letrozole, Animals, Antineoplastic Agents, Dose-Response Relationship, Drug, Estradiol, Estrogen Antagonists, Female, Humans, Mammary Neoplasms, Experimental, Mice, Transgenic, Nitriles, Ovariectomy, Triazoles, Mice, Knockout, Estrogen Receptor alpha, Cell Proliferation, Wnt1 Protein, Mice

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Effects of estrogen on breast cancer development: Role of estrogen receptor independent mechanisms

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