Breast Cancer

, Volume 26, Issue 4, pp 459–470 | Cite as

Cancer stem-like properties of hormonal therapy-resistant breast cancer cells

  • Kanami Uchiumi
  • Kouki Tsuboi
  • Nozomi Sato
  • Takako Ito
  • Hisashi Hirakawa
  • Toshifumi Niwa
  • Yuri Yamaguchi
  • Shin-ichi HayashiEmail author
Original Article



Presently, hormonal therapy targeting estrogen receptors is the most effective treatment available for luminal breast cancer. However, many patients relapse after the therapy. It has been suggested that cancer stem-like cells are involved with hormonal therapy resistance; in the present study, we evaluated this hypothesis.


In the present study, we used our previously established hormonal therapy-resistant cell lines, including aromatase inhibitor (AI)-resistant cells (Type 1 and Type 2) and fulvestrant-resistant cells (MFR).


AI-resistant cell lines expressing ER (Type 1 V1 and V2) showed high cancer stemness in terms of their CD44/CD24 expression and side populations, which were stimulated by the addition of estrogen and inhibited by fulvestrant. However, ALDH activity was lower than in the ER-negative resistant cells, suggesting that the stemness of luminal cells is distinct from that of basal-like breast cancer cells. The migration and invasion activity of the ER-positive Type 1 V1 and V2 cells were higher than in the ER-negative cell lines, Type 2 and MFR.


Fractionation of parental cells based on CD44/CD24 expression and colony formation assay indicated that CD44+/CD24+ cells might be the origin of hormonal therapy-resistant cells. This population reconstituted various other subpopulations under estrogen deprivation. These results indicate that hormonal therapy resistance is closely related to the cancer stem cell-like properties of luminal breast cancer.


Breast cancer Hormonal therapy resistance Cancer stem-like cells Estrogen receptor 



This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan, a Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan, the Program for Promotion of Fundamental Studies in Health Science of the National Institute of Biomedical Innovation (NIBIO), and a grant from the Smoking Research Foundation.

Compliance with ethical standards

Conflict of interest

Shin-ichi Hayashi received research grants from Novartis Pharma K.K, Astra Zeneca K.K, and Eisai K.K.

Supplementary material

12282_2018_944_MOESM1_ESM.docx (253 kb)
Supplementary material 1 (DOCX 252 KB)
12282_2018_944_MOESM2_ESM.docx (15 kb)
Supplementary material 2 (DOCX 15 KB)


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Copyright information

© The Japanese Breast Cancer Society 2019

Authors and Affiliations

  • Kanami Uchiumi
    • 1
  • Kouki Tsuboi
    • 1
  • Nozomi Sato
    • 1
  • Takako Ito
    • 2
  • Hisashi Hirakawa
    • 3
  • Toshifumi Niwa
    • 1
  • Yuri Yamaguchi
    • 4
  • Shin-ichi Hayashi
    • 1
    Email author
  1. 1.Department of Molecular and Functional Dynamics, Graduate School of MedicineTohoku UniversitySendaiJapan
  2. 2.Department of Blood and Cell TreatmentTohoku University HospitalSendaiJapan
  3. 3.Department of SurgeryTohoku Kosai HospitalSendaiJapan
  4. 4.Research Institute for Clinical OncologySaitama Cancer CenterSaitamaJapan

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