A Novel Metastatic Estrogen Receptor-Expressing Breast Cancer Model with Antiestrogen Responsiveness

Most women diagnosed with breast cancer (BC) have estrogen receptor alpha-positive (ER+) disease. The current mouse models of ER+ BC often rely on exogenous estrogen to encourage metastasis, which modifies the immune system and the function of some tissues like bone. Other studies use genetically mo...

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Bibliographic Details
Published in:Cancers 2023-12, Vol.15 (24), p.5773
Main Authors: Langsten, Kendall L, Shi, Lihong, Wilson, Adam S, Lumia, Salvatore, Westwood, Brian, Skeen, Alexandra M, Xie, Maria T, Surratt, Victoria E, Turner, JoLyn, Langefeld, Carl D, Singh, Ravi, Cook, Katherine L, Kerr, Bethany A
Format: Article
Language:English
Subjects:
Animal models
Antibiotics
Antiestrogens
Bones
Breast cancer
Cells
Cloning
Estrogen
Estrogen receptors
Estrogens
Ethylenediaminetetraacetic acid
Genetically modified organisms
Immune system
Immunocompetence
Immunosuppressive agents
Medical research
Metastases
Metastasis
Phenols
Proteins
Tamoxifen
Therapeutic applications
Tumor cell lines
Tumors
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Summary:Most women diagnosed with breast cancer (BC) have estrogen receptor alpha-positive (ER+) disease. The current mouse models of ER+ BC often rely on exogenous estrogen to encourage metastasis, which modifies the immune system and the function of some tissues like bone. Other studies use genetically modified or immunocompromised mouse strains, which do not accurately replicate the clinical disease. To create a model of antiestrogen responsive BC with spontaneous metastasis, we developed a mouse model of 4T1.2 triple-negative (TN) breast cancer with virally transduced ER expression that metastasizes spontaneously without exogenous estrogen stimulation and is responsive to antiestrogen drugs. Our mouse model exhibited upregulated ER-responsive genes and multi-organ metastasis without exogenous estrogen administration. Additionally, we developed a second TN BC cell line, E0771/bone, to express ER, and while it expressed ER-responsive genes, it lacked spontaneous metastasis to clinically important tissues. Following antiestrogen treatment (tamoxifen, ICI 182,780, or vehicle control), 4T1.2- and E0771/bone-derived tumor volumes and weights were significantly decreased, exemplifying antiestrogen responsivity in both cell lines. This 4T1.2 tumor model, which expresses the estrogen receptor, metastasizes spontaneously, and responds to antiestrogen treatment, will allow for further investigation into the biology and potential treatment of metastasis.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15245773