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Mol Cell Endocrinol. 2016 Feb 15;422:160-171. doi: 10.1016/j.mce.2015.11.033. Epub 2015 Dec 13.

GPER1-mediated IGFBP-1 induction modulates IGF-1-dependent signaling in tamoxifen-treated breast cancer cells.

Author information

1
Molecular Biology Program, New Mexico State University, Las Cruces, NM 88003, USA.
2
Molecular Biology Program, New Mexico State University, Las Cruces, NM 88003, USA; Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM 88003, USA. Electronic address: khouston@nmsu.edu.

Abstract

Tamoxifen, a selective estrogen receptor modulator, is a commonly prescribed adjuvant therapy for estrogen receptor-α (ERα)-positive breast cancer patients. To determine if extracellular factors contribute to the modulation of IGF-1 signaling after tamoxifen treatment, MCF-7 cells were treated with IGF-1 in conditioned medium (CM) obtained from 4-OHT-treated MCF-7 cells and the accumulation of phospho-Akt (S473) was measured. CM inhibited IGF-1-dependent cell signaling and suggesting the involvement of extracellular factors (ie. IGFBPs). A significant increase in IGFBP-1 mRNA and extracellular IGFBP-1 protein was observed in 4-OHT-treated MCF-7 cells. Knockdown experiments demonstrated that both GPER1 and CREB mediate IGFBP-1 induction. Furthermore, experiments showed that 4-OHT-dependent IGFBP-1 transcription is downstream of GPER1-activation in breast cancer cells. Additionally, neutralization and knockdown experiments demonstrated a role for IGFBP-1 in the observed inhibition of IGF-1 signaling. These results suggested that 4-OHT inhibits IGF-1 signaling via GPER1 and CREB mediated extracellular IGFBP-1 accumulation in breast cancer cells.

KEYWORDS:

Breast cancer; GPER1; IGF-1; IGFBP-1; Tamoxifen

PMID:
26690777
PMCID:
PMC4742395
DOI:
10.1016/j.mce.2015.11.033
[Indexed for MEDLINE]
Free PMC Article

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