ArticleBreast cancer research and treatment2008
Amphiregulin-EGFR signaling regulates PTHrP gene expression in breast cancer cells.
Article in Breast cancer research and treatment, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- Does the ERBB/EGF Signaling Network Serve as a Nexus for Oncogenic Signals in Uveal Melanoma?Biomolecules · 2026Review
- The Epidermal Growth Factor Receptor (EGFR) as a means of neuro-immune cross-conversation.Journal of neuroinflammation · 2026Review
- Indenoquinoxaline-Based Spiro-Heterocycles: Synthesis, Structural Characterization, MEDT Study, and Dual Inhibition of Kinase-Related Enzymes EGFR and VEGFR2.Chemistry & biodiversity · 2026Article
- Amphiregulin in Fibrotic Diseases and Cancer.International journal of molecular sciences · 2025Review
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- Oxidised IL-33 drives COPD epithelial pathogenesisThe European respiratory journal · 2023Article
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- Inhibition of epidermal growth factor receptor suppresses parathyroid hormone-related protein expression in tumours and ameliorates cancer-associated cachexia.Journal of cachexia, sarcopenia and muscle · 2022Article
- The Yin and Yang of ERBB4: Tumor Suppressor and Oncoprotein.Pharmacological reviews · 2022Review
- Review
- Proteolytic Regulation of Parathyroid Hormone-Related Protein: Functional Implications for Skeletal Malignancy.International journal of molecular sciences · 2019Review
- Time-dependent antagonist-agonist switching in receptor tyrosine kinase-mediated signaling.BMC bioinformatics · 2019Article
- A Macrophage-Pericyte Axis Directs Tissue Restoration via Amphiregulin-Induced Transforming Growth Factor Beta Activation.Immunity · 2019Article
- Different Epidermal Growth Factor Receptor (EGFR) Agonists Produce Unique Signatures for the Recruitment of Downstream Signaling Proteins.The Journal of biological chemistry · 2016Article
- Wild-type and specific mutant androgen receptor mediates transcription via 17β-estradiol in sex hormone-sensitive cancer cells.Journal of cellular physiology · 2015Article
- BMP9 regulates cross-talk between breast cancer cells and bone marrow-derived mesenchymal stem cells.Cellular oncology (Dordrecht, Netherlands) · 2014Article
- Molecular pathogenesis of bone metastases in breast cancer: Proven and emerging therapeutic targets.World journal of clinical oncology · 2014Review
- Tumor microenvironment regulates metastasis and metastasis genes of mouse MMTV-PymT mammary cancer cells in vivo.Veterinary pathology · 2014Article
- Influence of terminal differentiation and PACAP on the cytokine, chemokine, and growth factor secretion of mammary epithelial cells.Journal of molecular neuroscience : MN · 2014Article
- Oestrogen increases the activity of oestrogen receptor negative breast cancer stem cells through paracrine EGFR and Notch signalling.Breast cancer research : BCR · 2013Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Parathyroid hormone-related protein (PTHrP) is an autocrine/paracrine factor produced by breast cancer cells that is speculated to play a major role in permitting breast cancer cells to grow into the bone microenvironment by stimulating the bone resorption axis. It has been previously shown that EGFR signaling induces the production of PTHrP in several primary and transformed epithelial cell types. Therefore, we investigated the relationship between EGFR and PTHrP gene expression in human breast cancer cells. Of a panel of 7 breast epithelial and cancer cell lines, the osteolytic, EGFR- positive lines (MDA-MB-231 and NS2T2A1) exhibited higher levels of PTHrP transcript expression. Amphiregulin mRNA levels in all lines were approximately 2 orders of magnitude higher than those of TGFalpha or HB-EGF. In the EGFR bearing lines, the receptor was phosphorylated at tyrosine 992 under basal conditions, and the addition of 100 nM amphiregulin did not lead to the phosphorylation of other tyrosine residues typically phosphorylated by the prototypical ligand EGF. Treatment of the EGFR positive lines with the EGFR inhibitor PD153035 and amphiregulin-neutralizing antibodies reduced PTHrP mRNA levels by 50-70%. Stable EGFR expression in the MCF7 line failed to increase basal PTHrP mRNA levels; however, treatment of this cell line with exogenous EGF or amphiregulin increased PTHrP transcription 3-fold. Transient transfection analysis suggests that the MAPK pathway and ETS transcription factors mediate EGFR coupling to PTHrP gene expression. Taken together, it appears that autocrine stimulation of EGFR signaling by amphiregulin is coupled to PTHrP gene expression via EGFR Tyr992 and MAPK, and that this pathway may contribute to PTHrP expression by breast tumor cells.
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