ArticleBreast cancer research : BCR2014
Aldehyde dehydrogenase and estrogen receptor define a hierarchy of cellular differentiation in the normal human mammary epithelium.
Article in Breast cancer research : BCR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 55 citations in OpenAlex.
- ALDH1A1 in breast cancer: A prospective target to overcome therapy resistance (Review).Oncology letters · 2025Review
- The Applicability and Limitations of the Spectrofluorometric Method for Determination of ALDH1 Activity in Serum and Plasma.Diagnostics (Basel, Switzerland) · 2024Article
- The Molecular Context of Oxidant Stress Response in Cancer Establishes ALDH1A1 as a Critical Target: What This Means for Acute Myeloid Leukemia.International journal of molecular sciences · 2023Review
- Transcriptome Analysis of Goat Mammary Gland Tissue Reveals the Adaptive Strategies and Molecular Mechanisms of Lactation and Involution.International journal of molecular sciences · 2022Article
- MUC1 is a potential target to overcome trastuzumab resistance in breast cancer therapy.Cancer cell international · 2022Review
- Fibroblasts direct differentiation of human breast epithelial progenitors.Breast cancer research : BCR · 2020Article
- Increased Expression of Interleukin-1 Receptor Characterizes Anti-estrogen-Resistant ALDHStem cell reports · 2020Article
- Endocrine Disruptor Bisphenol A (BPA) Triggers Systemic Para-Inflammation and is Sufficient to Induce Airway Allergic Sensitization in Mice.Nutrients · 2020Article
- Role of Vitamin A in Mammary Gland Development and Lactation.Nutrients · 2019Review
- A CD146 FACS Protocol Enriches for Luminal Keratin 14/19 Double Positive Human Breast Progenitors.Scientific reports · 2019Article
- P-cadherin mutations are associated with high basal Wnt activity and stemness in canine mammary tumor cell lines.Oncotarget · 2019Article
- Heterogeneity of Human Breast Stem and Progenitor Cells as Revealed by Transcriptional Profiling.Stem cell reports · 2018Article
- Obesity reversibly depletes the basal cell population and enhances mammary epithelial cell estrogen receptor alpha expression and progenitor activity.Breast cancer research : BCR · 2017Article
- SOX11 promotes invasive growth and ductal carcinoma in situ progression.The Journal of pathology · 2017Article
- Alteration of Mammary Gland Development and Gene Expression by In Utero Exposure to Cadmium.International journal of molecular sciences · 2017Article
- Article
- How interacting pathways are regulated by miRNAs in breast cancer subtypes.BMC bioinformatics · 2016Article
- FOXA1 expression affects the proliferation activity of luminal breast cancer stem cell populations.Cancer science · 2016Article
- The absence of aldehyde dehydrogenase 1 A1-positive cells in benign mammary stroma is associated with risk factors for breast cancer.Breast cancer (Dove Medical Press) · 2016Article
- Propagation of oestrogen receptor-positive and oestrogen-responsive normal human breast cells in culture.Nature communications · 2015Article
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Authors and funding
13 authors at 5 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionAlthough estrogen and progesterone play a key role in normal mammary development and in breast cancer, the potential for proliferation and lineage differentiation as well as origin of cells that express the estrogen receptor (ER) in normal breast epithelium are not known. Some evidence suggests that normal human mammary stem/progenitor cells are ER-, but the identity of these cells and the cellular hierarchy of breast epithelium are still subjects of controversy. It is likely that elucidation of these aspects will bring insight into the cellular origin of breast cancer subtypes.
methodsWe used fluorescence-activated cell sorting of primary human mammary epithelial cells along with in vitro and in vivo functional assays to examine the hierarchic relation between cells with aldehyde dehydrogenase enzymatic activity (ALDH+ cells) and ER+ cells in the normal human breast epithelium. We assessed the proliferation and lineage differentiation potential of these cells in vitro and in vivo. A gene reporter assay was used to separate live ER+ and ER- mammary epithelial cells. With shRNA-mediated knockdown, we investigated the role of ALDH isoforms in the functionality of mammary epithelial progenitor cells.
resultsWe describe a cellular hierarchy in the normal human mammary gland in which ER-/ALDH+ cells with functional properties of stem/progenitor cells generate ER+ progenitor cells, which in turn give rise to cells of luminal lineage. We show that the ALDH1A1 isoform, through its function in the retinoic acid metabolism, affects the proliferation and/or early differentiation of stem/progenitor cells and is important for branching morphogenesis.
conclusionsThis study presents direct evidence that ER+ cells are generated by ER-/ALDH+ stem/progenitor cells. We also show that ER+ cells are able to generate cell progeny of luminal lineage in vitro and in vivo. Loss of ALDH1A1 function impairs this process, as well as branching morphogenesis and clonogenicity in suspension culture. This latter effect is reversed by treatment with retinoic acid.
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