Insulin-like growth factor-binding protein-3 is induced by tamoxifen and fulvestrant and modulates fulvestrant response in breast cancer cells
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View abstract on PubMed
Summary
This summary is machine-generated.Insulin-like growth factor binding protein-3 (IGFBP-3) has opposing effects in breast cancer subtypes. It inhibits ERα-positive cells but promotes triple-negative breast cancer (TNBC) growth, potentially mediating antiestrogen response.
Area Of Science
- Endocrinology
- Oncology
- Molecular Biology
Background
- Insulin-like growth factor binding protein-3 (IGFBP-3) exhibits differential roles in estrogen receptor alpha (ERα)-positive and triple-negative breast cancer (TNBC).
- In ERα-positive breast cancer, IGFBP-3 acts as an antiproliferative and proapoptotic factor.
- Conversely, in TNBC, IGFBP-3 promotes cell proliferation through epidermal growth factor receptor (EGFR) activation.
Purpose Of The Study
- To elucidate the mechanisms behind the contrasting effects of IGFBP-3 on ERα-positive and TNBC cells.
- To investigate the modulation of IGFBP-3 expression by antiestrogens and its impact on breast cancer cell behavior.
Main Methods
- Assessed IGFBP-3 expression in ERα-positive (MCF-7, T-47D) and TNBC (MDA-MB-231, MDA-MB-468) cell line models.
- Treated cells with antiestrogens tamoxifen and fulvestrant, a GPER1 agonist (G-1), and a YAP/TAZ inhibitor (P17).
- Examined the effects of IGFBP-3 expression and antiestrogen treatment on cell proliferation and resistance.
Main Results
- MCF-7 and T-47D cells showed lower IGFBP-3 levels than MDA-MB-231 and MDA-MB-468 cells.
- Fulvestrant-resistant MCF-7 cells exhibited high IGFBP-3 expression, indicating a link between IGFBP-3 and resistance.
- Tamoxifen and fulvestrant increased IGFBP-3 expression in all cell lines and enhanced TNBC proliferation.
- G-1 treatment upregulated IGFBP-3, while P17 treatment attenuated it.
Conclusions
- IGFBP-3 plays a significant role in modulating breast cancer cell behavior across different subtypes.
- IGFBP-3 expression is influenced by antiestrogen therapy and G-protein coupled estrogen receptor 1 (GPER1) signaling.
- IGFBP-3 acts as a mediator in the cellular response to tamoxifen and fulvestrant, impacting treatment outcomes.
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