ArticleCancer research2008
The role of amphiregulin in exemestane-resistant breast cancer cells: evidence of an autocrine loop.
Article in Cancer research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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.
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Who cites it
27 citing papers in PubMed, 62 citations in OpenAlex.
- A review of epidermal growth factor receptor ligands in glucose homeostasis.Frontiers in endocrinology · 2026Review
- Dynamic dual regulation of amphiregulin in liver pathophysiology: balancing regeneration and disease progression via the EGFR axis.Frontiers in medicine · 2026Review
- Olaparib synergy screen reveals Exemestane induces replication stress in triple-negative breast cancer.Molecular oncology · 2025Article
- CITED1 as a marker of favourable outcome in anti-endocrine treated, estrogen-receptor positive, lymph-node negative breast cancer.BMC research notes · 2023Article
- Article
- An Exemestane Derivative, Oxymestane-D1, as a New Multi-Target Steroidal Aromatase Inhibitor for Estrogen Receptor-Positive (ERMolecules (Basel, Switzerland) · 2023Article
- Role of Exemestane in the Treatment of Estrogen-Receptor-Positive Breast Cancer: A Narrative Review of Recent Evidence.Advances in therapy · 2022Review
- Effects of PI3K inhibition in AI-resistant breast cancer cell lines: autophagy, apoptosis, and cell cycle progression.Breast cancer research and treatment · 2021Article
- Amphiregulin retains ERα expression in acquired aromatase inhibitor resistant breast cancer cells.Endocrine-related cancer · 2020Article
- Heregulin Drives Endocrine Resistance by Altering IL-8 Expression in ER-Positive Breast Cancer.International journal of molecular sciences · 2020Article
- Valproic acid-induced amphiregulin secretion confers resistance to temozolomide treatment in human glioma cells.BMC cancer · 2019Article
- Triiodothyronine Promotes Cell Proliferation of Breast Cancer via Modulating miR-204/Amphiregulin.Pathology oncology research : POR · 2019Article
- Novel and Alternative Targets Against Breast Cancer Stemness to Combat Chemoresistance.Frontiers in oncology · 2019Review
- Amphiregulin Is a Critical Downstream Effector of Estrogen Signaling in ERα-Positive Breast Cancer.Cancer research · 2015Article
- New cell culture model for aromatase inhibitor-resistant breast cancer shows sensitivity to fulvestrant treatment and cross-resistance between letrozole and exemestane.International journal of oncology · 2015Article
- MicroRNA-125b upregulation confers aromatase inhibitor resistance and is a novel marker of poor prognosis in breast cancer.Breast cancer research : BCR · 2015Article
- Amphiregulin and PTEN evoke a multimodal mechanism of acquired resistance to PI3K inhibition.Genes & cancer · 2014Article
- The effects of amphiregulin induced MMP-13 production in human osteoarthritis synovial fibroblast.Mediators of inflammation · 2014Article
- Mechanisms of resistance to endocrine therapy in breast cancer: focus on signaling pathways, miRNAs and genetically based resistance.International journal of molecular sciences · 2012Review
- Nuclear translocation of pro-amphiregulin induces chemoresistance in gastric cancer.Cancer science · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Exemestane-resistant breast cancer cell lines (i.e., ExeR), derived from MCF-7 cells expressing a high level of aromatase (MCF-7aro), were generated in our laboratory. The epidermal growth factor (EGF)-like protein amphiregulin (AREG) was highly expressed in ExeR cells based on cDNA microarray analysis. The high levels of AREG mRNA in ExeR cell lines were confirmed by real-time reverse transcription-PCR. The high levels of AREG protein in ExeR cell lysates and culture media were confirmed by Western blot analysis and ELISA, respectively. Furthermore, our Western blot analysis showed that whereas no AREG was detected in the DMSO control, overnight treatment of parental MCF-7aro cells with 1 micromol/L exemestane strongly induced the expression of AREG. This induction was totally blocked by 100 nmol/L of pure antiestrogen ICI 182,780, implying estrogen receptor (ER) dependence of exemestane-induced AREG expression. MCF-7aro cells were not able to proliferate in hormone-free medium, but were able to proliferate in conditioned medium from ExeR cells, similar to the treatment of recombinant human AREG. Small interference RNA targeting AREG inhibited ExeR proliferation, confirming that AREG is truly functioning as a growth factor of ExeR cells. The specific inhibitors to ER (ICI 182,780), EGF receptor (EGFR; AG1478), and mitogen-activated protein kinase (MAPK; U0126) all showed dose-dependent suppression of the proliferation of ExeR cells, indicating the involvement of the ER, EGFR, and MAPK pathways. Based on these findings, we propose a possible mechanism that underlies exemestane resistance: exemestane induces AREG in an ER-dependent manner. AREG then activates the EGFR pathway and leads to the activation of the MAPK pathway that drives cell proliferation.
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Registered trials
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.