Effect of 17β-estradiol on estrogen receptor negative breast cancer cells in an osteolytic mouse model

D Joshua Cohen; Vaidehi Patel; Anjali Verma; Barbara D Boyan; Zvi Schwartz

doi:10.1016/j.steroids.2017.10.010

Effect of 17β-estradiol on estrogen receptor negative breast cancer cells in an osteolytic mouse model

Steroids. 2019 Feb:142:28-33. doi: 10.1016/j.steroids.2017.10.010. Epub 2017 Nov 10.

Authors

D Joshua Cohen¹, Vaidehi Patel², Anjali Verma², Barbara D Boyan³, Zvi Schwartz⁴

Affiliations

¹ Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
² Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA.
³ Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA. Electronic address: bboyan@vcu.edu.
⁴ Department of Biomedical Engineering, School of Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA; Department of Periodontics, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.

PMID: 29133279
DOI: 10.1016/j.steroids.2017.10.010

Abstract

17β-Estradiol (E2) promotes metastasis of triple negative breast cancer cells to bone. Recent studies show many triple negative breast cancer cell lines lacking the 66 kDa estrogen receptor (ER) alpha (ERα66) or its splice variant ERα46, express another splice variant, ERα36 associated with membrane-mediated rapid actions of the hormone. qPCR and western blot confirmed that MCF7 cells possessed ERα splice variants ERα66, ERα46 and ERα36, while ER-negative breast cancer cells MDA-MB-231 possessed only ERα36. MDA-MB-231 breast cancer cells were implanted into medullary canals of ovariectomized female athymic nude mice femurs (N = 8 mice/treatment). To examine the effect of E2 on osteolysis, mice were treated with 0.72 mg E2 or placebo via 60 day release osmotic pumps implanted subcutaneously. Legs were examined by Faxitron through the course of the study, and by microCT and histology after 8 weeks. Greater occurrence of osteolysis and pathologic fracture was observed in E2-treated animals compared to placebo, and microCT demonstrated less bone volume remaining in MDA-MB-231 treated legs compared to contralateral control legs, as well as E2-treated animals compared to placebo. E2-treated animals had significantly greater tumor volume compared to placebo. Large nests of anaplastic tumor cells with eroded cortical margin were observed in E2-treated animals compared to placebo. MDA MB 231 breast cancer cells positive for ERα36 but negative for ERα46/66 had enhanced osteolysis, pathologic fractures, and tumor volume in an in vivo osteolytic mouse model when treated with 17β-estradiol compared to placebo, demonstrating a role for ERα36 in bone tumor progression.

Keywords: Animal model; Breast cancer; ERα36; Osteolysis.

MeSH terms

Animals
Breast Neoplasms / metabolism*
Breast Neoplasms / pathology
Disease Models, Animal*
Dose-Response Relationship, Drug
Estradiol / pharmacology*
Female
Humans
MCF-7 Cells
Mice
Mice, Nude
Osteolysis / metabolism*
Osteolysis / pathology
Receptors, Estrogen / deficiency*
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Receptors, Estrogen
Estradiol