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

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.

journal_name

Clin Breast Cancer

journal_title

Clinical breast cancer

authors

Ito T,Sato N,Yamaguchi Y,Tazawa C,Moriya T,Hirakawa H,Hayashi S

doi

10.1016/j.clbc.2014.11.002

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

e93-103

issue

2

eissn

1526-8209

issn

1938-0666

pii

S1526-8209(14)00249-3

journal_volume

15

pub_type

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