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GPER1-mediated IGFBP-1 induction modulates IGF-1-dependent signaling in tamoxifen-treated breast cancer cells
- Source :
- Molecular and Cellular Endocrinology. 422:160-171
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
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.
- Subjects :
- 0301 basic medicine
Cell signaling
medicine.medical_specialty
Cell Culture Techniques
Estrogen receptor
Breast Neoplasms
CREB
Biochemistry
Article
Receptors, G-Protein-Coupled
03 medical and health sciences
0302 clinical medicine
Breast cancer
Endocrinology
Cell Line, Tumor
Internal medicine
medicine
Extracellular
Humans
Insulin-Like Growth Factor I
Phosphorylation
Cyclic AMP Response Element-Binding Protein
Molecular Biology
Gene knockdown
biology
Chemistry
medicine.disease
3. Good health
Insulin-Like Growth Factor Binding Protein 1
Tamoxifen
030104 developmental biology
Receptors, Estrogen
Selective estrogen receptor modulator
Culture Media, Conditioned
030220 oncology & carcinogenesis
MCF-7 Cells
biology.protein
Cancer research
Female
Hydroxytestosterones
Proto-Oncogene Proteins c-akt
hormones, hormone substitutes, and hormone antagonists
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 03037207
- Volume :
- 422
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Endocrinology
- Accession number :
- edsair.doi.dedup.....950f9b21055fbfb5b78a6a4d9cdfbd02
- Full Text :
- https://doi.org/10.1016/j.mce.2015.11.033