ArticleBreast cancer research and treatment2017
Downregulation of estrogen receptor and modulation of growth of breast cancer cell lines mediated by paracrine stromal cell signals.
Article in Breast cancer research and treatment, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Outlook and opportunities for engineered environments of breast cancer dormancy.Science advances · 2024Review
- Mechanisms of endocrine resistance in hormone receptor-positive breast cancer.Frontiers in oncology · 2024Review
- Mathematical reconstruction of the metabolic network in an in-vitro multiple myeloma model.PLoS computational biology · 2023Article
- Review
- Effects of iron modulation on mesenchymal stem cell-induced drug resistance in estrogen receptor-positive breast cancer.Oncogene · 2022Article
- Estrogen Receptor Alpha and ESR1 Mutations in Breast Cancer.Advances in experimental medicine and biology · 2022Article
- Breast cancer: molecular mechanisms of underlying resistance and therapeutic approaches.American journal of cancer research · 2022Review
- Syngeneic tobacco carcinogen-induced mouse lung adenocarcinoma model exhibits PD-L1 expression and high tumor mutational burden.JCI insight · 2021Article
- Autophagy and Cancer Dormancy.Frontiers in oncology · 2021Review
- Intrinsic and Extrinsic Factors Governing the Transcriptional Regulation of ESR1.Hormones & cancer · 2020Review
- Modeling chemical effects on breast cancer: the importance of the microenvironment in vitro.Integrative biology : quantitative biosciences from nano to macro · 2020Review
- Bone Marrow Stromal Cells Transcriptionally Repress ESR1 but Cannot Overcome Constitutive ESR1 Mutant Activity.Endocrinology · 2019Article
- IL-1 induces p62/SQSTM1 and autophagy in ERαJournal of cellular biochemistry · 2019Article
- Estrogen Receptor Beta Inhibits The Proliferation, Migration, And Angiogenesis Of Gastric Cancer Cells Through Inhibiting Nuclear Factor-Kappa B Signaling.OncoTargets and therapy · 2019Article
- The Tumor Microenvironment as a Regulator of Endocrine Resistance in Breast Cancer.Frontiers in endocrinology · 2019Review
- Signaling pathways and steroid receptors modulating estrogen receptor α function in breast cancer.Genes & development · 2018Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeBreast cancers have a poorer prognosis if estrogen receptor expression was lost during recurrence. It is unclear whether this conversion is cell autonomous or whether it can be promoted by the microenvironment during cancer dormancy. We explored the ability of marrow-derived stromal cell lines to arrest co-cultured breast cancer cells and suppress estrogen receptor alpha (ER) expression during arrest, facilitating the emergence of estrogen-independent breast cancer clones.
methodsCancer cell growth, ER protein, microRNA, and mRNA levels were measured in breast cancer cell lines exposed to conditioned medium from marrow stromal lines in the presence and absence of estrogen and of signaling pathway modulators.
resultsWe demonstrate that paracrine signaling from the stromal cell line HS5 downregulated ER in T47D and MCF7 breast cancer cells. This occurred at the mRNA level and also through decreased ER protein stability. Additionally, conditioned medium (CM) from HS5 arrested the breast cancer cells in G0/G1 in part through interleukin-1 (IL1) and inhibited cancer cell growth despite the activation of proliferative pathways (Erk and AKT) by the CM. Similar findings were observed for CM from the hFOB 1.19 osteoblastic cell line but not from two other fibroblastic marrow lines, HS27A and KM101. HS5-CM inhibition of MCF7 proliferation could not be restored by exogenous ER, but was restored by the IL1-antagonist IL1RA. In the presence of IL1RA, HS5-CM activation of AKT and Erk enabled the outgrowth of breast cancer cells with suppressed ER that were fulvestrant-resistant and estrogen-independent.
conclusionsWe conclude that marrow-derived stromal cells can destabilize estrogen receptor protein to convert the ER status of growth-arrested ER+ breast cancer cell lines. The balance between stromal pro- and anti-proliferative signals controlled the switch from a dormant phenotype to estrogen-independent cancer cell growth.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.