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10:51
Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Crosstalk between EGFR and extranuclear steroid receptors
Antimo Migliaccio1, Gabriella Castoria, Marina Di Domenico
1Dipartimento di Patologia Generale, Facoltà di Medicina e Chirurgia, II Università di Napoli, Via L. De Crecchio, 7-80138 Naples, Italy.
Annals of the New York Academy of Sciences
|January 31, 2007
Summary
Epidermal growth factor (EGF) triggers cancer cell growth by activating estrogen (ER) and androgen (AR) receptors. Inhibiting this crosstalk with antagonists or blocking the Src kinase halts EGF
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Epidermal growth factor (EGF) is known to stimulate cancer cell proliferation.
- Estrogen (ER) and androgen (AR) receptors play roles in hormone-dependent cancers.
- Crosstalk between growth factor signaling and steroid hormone receptors is increasingly recognized.
Purpose of the Study:
- To investigate the molecular mechanisms underlying EGF action in breast and prostate cancer cells.
- To determine the role of estrogen and androgen receptors in EGF-stimulated signaling pathways.
- To elucidate the involvement of the Src kinase in the crosstalk between EGF and steroid hormone receptors.
Main Methods:
- Utilized human breast cancer (MCF-7) and prostate cancer (LNCaP) cell lines.
- Administered EGF, estrogen (ICI 182,780), and androgen (Casodex) antagonists.
- Employed siRNA for receptor silencing and PP2 inhibitor for Src kinase inhibition.
- Analyzed EGFR and ER phosphorylation and complex formation using biochemical assays.
Main Results:
- EGF stimulates DNA synthesis and cytoskeletal rearrangement in MCF-7 and LNCaP cells.
- Estrogen and androgen antagonists inhibit EGF-induced effects, indicating receptor involvement.
- EGF promotes the formation of a complex involving EGFR, AR/ER, and Src kinase.
- This complex formation is essential for Src activity, EGFR phosphorylation, and EGF signaling pathway activation.
Conclusions:
- A functional crosstalk exists between EGF and ER/AR signaling pathways in breast and prostate cancer cells.
- The AR/ER/Src complex is crucial for mediating EGF-dependent cellular responses.
- Targeting this complex or its components may offer therapeutic strategies for hormone-responsive cancers.
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