Differences in stemness properties associated with the heterogeneity of luminal-type breast cancer

Takako Ito, Nozomi Sato, Yuri Yamaguchi, Chika Tazawa, Takuya Moriya, Hisashi Hirakawa, Shin Ichi Hayashi

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Background Luminal-type breast cancers are the most abundant subtype. Endocrine therapies targeting estrogen receptor (ER) or estradiol (E2) synthesis have achieved marked improvement in disease-free and overall survival of ER-positive cancers. However, approximately one-third of these cancers are poorly responsive to endocrine therapies, suggesting nonuniform tumor cell characteristics of this subtype. Recently, the tumorigenesis theory which states that CSCs are capable of self-renewal, tumorigenicity, and therapeutic resistance, became widely accepted. We investigated the relationship between the heterogeneity of luminal-type breast cancer and stemness properties. Materials and Methods CSC surface markers and expression of stemness-related genes, including Octamer-binding transcription factor 4 (OCT4), Nanog homeobox (NANOG), and Kruppel-like factor 4 (KLF4), were analyzed in clinical samples. ER activities were analyzed using the adenovirus vector carrying the ERE-green fluorescent protein (GFP). We separated the luminal-type breast cancers into 2 groups according to stemness-related gene expression patterns in mammospheres. Results The group that predominantly expressed NANOG mRNA showed a high percentage of the cells that were positive for CD44 and negative for CD24 and Hoechst (possessing high-stemness properties), younger patient age, higher p53 expression, and tended to show higher histological grade and higher topoisomerase IIα expression. The ERE-GFP assay revealed that the luminal-type breast cancer mammospheres were heterogeneous. Mammospheres from several specimens lacked ER activity and responsiveness to E2 but some retained ER activities. Conclusion ERE activity differences might be associated with endocrine therapy effectiveness. Mammosphere stemness properties could be a useful and novel criterion for subclassification of luminal-type breast cancers.

Original languageEnglish
Pages (from-to)e93-e103
JournalClinical Breast Cancer
Volume15
Issue number2
DOIs
Publication statusPublished - 2015 Apr 1

Keywords

  • Cancer stem cells
  • Estrogen response element activity
  • Mammosphere
  • Primary breast cancer
  • Stemness-related genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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