ArticlePloS one2013
Distinct effects of EGFR ligands on human mammary epithelial cell differentiation.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed.
- Targeting the Epidermal Growth Factor Receptor Pathway in Chemotherapy-Resistant Triple-Negative Breast Cancer: A Phase II Study.Cancer research communications · 2024Trial
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- Differential ErbB receptor dimerization modulates the ability of EGF receptor ligands to regulate metabolic flux.The Journal of biological chemistry · 2026Article
- Article
- EGF receptor in organ development, tissue homeostasis and regeneration.Journal of biomedical science · 2025Review
- Revealing gene expression links between milk fat globules and mammary glands in rodents via transcriptomics.Frontiers in veterinary science · 2025Article
- Secretion of WNT7A by UC-MSCs assist in promoting the endometrial epithelial regeneration.iScience · 2024Article
- Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers.Nature communications · 2024Article
- Cell type and stage specific transcriptional, chromatin and cell-cell communication landscapes in the mammary gland.Heliyon · 2023Article
- ERBB Receptors and Their Ligands in the Developing Mammary Glands of Different Species: Fifteen Characters in Search of an Author.Journal of mammary gland biology and neoplasia · 2023Review
- Amphiregulin regulates odontogenic differentiation of dental pulp stem cells by activation of mitogen-activated protein kinase and the phosphatidylinositol 3-kinase signaling pathways.Stem cell research & therapy · 2022Article
- ORIGINS: A protein network-based approach to quantify cell pluripotency from scRNA-seq data.MethodsX · 2022Article
- Identification and functional analysis of mFrontiers in cell and developmental biology · 2022Article
- Transcriptome Profile Analysis of Triple-Negative Breast Cancer Cells in Response to a Novel Cytostatic Tetrahydroisoquinoline Compared to Paclitaxel.International journal of molecular sciences · 2021Article
- Unraveling Heterogeneity in Epithelial Cell Fates of the Mammary Gland and Breast Cancer.Cancers · 2019Review
- Time profile of nimotuzumab for enhancing radiosensitivity of the Eca109 cell line.Oncology letters · 2019Article
- Characterization of miRNA profiles in the mammary tissue of dairy cattle in response to heat stress.BMC genomics · 2018Article
- Early clinical development of epidermal growth factor receptor targeted therapy in breast cancer.Expert opinion on investigational drugs · 2017Review
- Casitas B-cell lymphoma (Cbl) proteins protect mammary epithelial cells from proteotoxicity of active c-Src accumulation.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Alpha fetoprotein plays a critical role in promoting metastasis of hepatocellular carcinoma cells.Journal of cellular and molecular medicine · 2016Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Based on gene expression patterns, breast cancers can be divided into subtypes that closely resemble various developmental stages of normal mammary epithelial cells (MECs). Thus, understanding molecular mechanisms of MEC development is expected to provide critical insights into initiation and progression of breast cancer. Epidermal growth factor receptor (EGFR) and its ligands play essential roles in normal and pathological mammary gland. Signals through EGFR is required for normal mammary gland development. Ligands for EGFR are over-expressed in a significant proportion of breast cancers, and elevated expression of EGFR is associated with poorer clinical outcome. In the present study, we examined the effect of signals through EGFR on MEC differentiation using the human telomerase reverse transcriptase (hTERT)-immortalized human stem/progenitor MECs which express cytokeratin 5 but lack cytokeratin 19 (K5(+)K19(-) hMECs). As reported previously, these cells can be induced to differentiate into luminal and myoepithelial cells under appropriate culture conditions. K5(+)K19(-) hMECs acquired distinct cell fates in response to EGFR ligands epidermal growth factor (EGF), amphiregulin (AREG) and transforming growth factor alpha (TGFα) in differentiation-promoting MEGM medium. Specifically, presence of EGF during in vitro differentiation supported development into both luminal and myoepithelial lineages, whereas cells differentiated only towards luminal lineage when EGF was replaced with AREG. In contrast, substitution with TGFα led to differentiation only into myoepithelial lineage. Chemical inhibition of the MEK-Erk pathway, but not the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, interfered with K5(+)K19(-) hMEC differentiation. The present data validate the utility of the K5(+)K19(-) hMEC cells for modeling key features of human MEC differentiation. This system should be useful in studying molecular/biochemical mechanisms of human MEC differentiation.
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