Uncoupling of the ERα regulated morphological phenotype from the cancer stem cell phenotype in human breast cancer cell lines.
The CD24(low/-)CD44(+)EpCAM(+) phenotype is associated with breast cancer initiating cells. To investigate if these putative breast cancer stem cell markers are regulated by estrogen receptor alpha (ERα) we have determined the expression levels of EpCAM, CD44 and CD24 in several well characterized breast cancer cell lines. The expression levels of the three adhesion proteins were quantitatively different in the cell lines but the composite CD24(low/-)CD44(+)EpCAM(+) breast cancer stem cell phenotype was shown to exist as a small fraction, between 0.1% and 1.2%, in all breast cancer cell lines tested. Experimental silencing of ERα resulted in a reduced epithelial appearance and partial reduction of CD24 mRNA, while levels of CD44 and EpCAM were unaltered. Moreover, knockdown of ERα led to a change in the morphology of the cells similar to the epithelial to mesenchymal transition phenotype and was associated with decreased E-cadherin expression. Our findings offer new insights into the regulation of the breast cancer stem cell phenotype by ERα and suggest that treatments targeting the breast cancer stem cell adhesion molecules and the ERα pathway may be complementary.
Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, R8:04, Karolinska University Hospital-Solna, 171 76 Stockholm, Sweden.
Salah-Eldin
SE
Gadalla
Anna
A
Alexandraki
Mikael S
MS
Lindström
Monica
M
Nistér
Christer
C
Ericsson
D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D000071858:Epithelial Cell Adhesion Molecule; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; D015820:Cadherins; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D047628:Estrogen Receptor alpha; D018960:Hyaluronan Receptors; D012333:RNA, Messenger