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Induction of anterior gradient 2 (AGR2) plays a key role in insulin-like growth factor-1 (IGF-1)-induced breast cancer cell proliferation and migration
- Source :
- Medical Oncology (Northwood, London, England)
- Publication Year :
- 2015
- Publisher :
- Springer US, 2015.
-
Abstract
- Anterior gradient 2 (AGR2) is a promising anti-tumor target associated with estrogen receptor expression and metastatic progression of breast cancer. Insulin-like growth factor-1 (IGF-1) is another potent factor that stimulates breast cancer progression and mediates anti-estrogen drug resistance. However, the precise mechanism and connections between these two factors in breast cancer drug resistance have not been fully elucidated. Here, for the first time, we decipher that IGF-1 remarkably induces AGR2 in the MCF7 cell line, through an estrogen response element (ERE) between −802 and −808 bp and a leucine zipper transcription factor-binding site located between −972 and −982 bp on the AGR2 promoter. We also found that the ERK1/2 and AKT pathways mediate estrogen receptor-α at the upstream of ERE and that the JNK pathway activates the leucine zipper site through the c-Jun/c-Fos complex. Additionally, our data suggest that knockdown of AGR2 reduces IGF-1-induced cell proliferation, migration and cell cycle progression. Therefore, we report that AGR2 is a key modulator involved in IGF-1-induced breast cancer development. We propose that the identification of the mechanism linking the IGF-1/insulin signal and AGR2 promoter activation is important, because it provides insights into the development of anti-breast cancer drugs.
- Subjects :
- medicine.medical_specialty
Leucine zipper
Cancer Research
MAP Kinase Signaling System
Proto-Oncogene Proteins c-jun
Estrogen receptor
AGR2
Breast Neoplasms
Biology
Breast cancer
Mucoproteins
Cell Movement
Internal medicine
Cell Line, Tumor
medicine
Humans
Insulin-Like Growth Factor I
Promoter Regions, Genetic
Transcription factor
Protein kinase B
Anterior gradient 2
Cell Proliferation
Oncogene Proteins
Original Paper
Leucine Zippers
Cell Cycle
Estrogen Receptor alpha
Activator protein-1 site
Genes, fos
Proteins
Estrogens
General Medicine
Hematology
medicine.disease
Endocrinology
Insulin-like growth factor-1
Oncology
Cancer research
MCF-7 Cells
Estrogen response element
Female
Signal transduction
Estrogen receptor alpha
Proto-Oncogene Proteins c-akt
Signal Transduction
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 1559131X and 13570560
- Volume :
- 32
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Medical Oncology (Northwood, London, England)
- Accession number :
- edsair.doi.dedup.....f38f24dbc385f6f58bb57b94b28629d1