Induction of anterior gradient 2 AGR2 plays a key role in insulin-like growth factor-1 IGF-1-induced breast cancer cell proliferation and migrationReportar como inadecuado




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 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Medical Oncology

, 32:178

First Online: 09 May 2015Received: 12 March 2015Accepted: 13 March 2015DOI: 10.1007-s12032-015-0577-z

Cite this article as: Li, Z., Wu, Z., Chen, H. et al. Med Oncol 2015 32: 178. doi:10.1007-s12032-015-0577-z

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.

KeywordsAnterior gradient 2 Insulin-like growth factor-1 Breast cancer Estrogen response element Activator protein-1 site Zheqi Li and Zhenghua Wu have contributed equally to this work.

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Autor: Zheqi Li - Zhenghua Wu - Hao Chen - Qi Zhu - Guangwei Gao - Lingyun Hu - Hema Negi - Suchitra Kamle - Dawei Li

Fuente: https://link.springer.com/



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