Interaction between IGF-IR and ER induced by E2 and IGF-I.

Abstract

Estrogen receptor (ER) is a nuclear receptor and the insulin-like growth factor-I (IGF-I) receptor (IGF-IR) is a transmembrane tyrosine kinase receptor. Estrogen and IGF-I are known to have synergistic effects on the growth of breast cancer cells. Recently, non-nuclear effects of ER have been under investigation. To study the mechanism involved in this process, we have used MCF-7 breast cancer cell lines transfected with IGF-IR anti-sense cDNA (SX13, MCF-7(SX13)) that resulted in 50% reduction of IGF-IR. In MCF-7 cells, estradiol (E2) and IGF-I induced the rapid association of ER to IGF-IR, however, the interaction was abrogated in MCF-7(SX13) cells. In addition, NWTB3 cells (NIH3T3 cells overexpressing IGF-IR) were transiently transfected with ERα, the ER-IGF-IR interaction was induced by both E2 and IGF-I. Moreover, ERα regulated the IGF-I signaling pathways through phosphorylation of ERK1/2 and Akt and the interaction of ER-IGF-IR potentiated the cell growth. Finally, E2 and IGF-I stimulated translocation of ER from the nucleus to the cytoplasm. Taken together, these findings reveal that the interaction of the ER and IGF-IR is important for the non-genomic effects of ER.

• Authors: Zhenghong Yu, Weimin Gao, Enze Jiang, Fang Lu, Luo Zhang, Zhaorong Shi, Xinxing Wang, Longbang Chen, Tangfeng Lv
• Journal: PloS one (PLoS One) Vol. 8 Issue 5 Pg. e62642 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23704881 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogen Receptor alpha
• Recombinant Fusion Proteins
• Green Fluorescent Proteins
• Estradiol
• Insulin-Like Growth Factor I
• Receptor, IGF Type 1
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Cell Nucleus (drug effects, metabolism)
• Cell Proliferation (drug effects)
• Estradiol (pharmacology)
• Estrogen Receptor alpha (metabolism)
• Green Fluorescent Proteins (metabolism)
• Humans
• Insulin-Like Growth Factor I (pharmacology)
• Intracellular Space (drug effects, metabolism)
• MCF-7 Cells
• Mice
• NIH 3T3 Cells
• Phosphorylation (drug effects)
• Protein Binding (drug effects)
• Protein Transport (drug effects)
• Proto-Oncogene Proteins c-akt (metabolism)
• Receptor, IGF Type 1 (metabolism)
• Recombinant Fusion Proteins (metabolism)
• Signal Transduction (drug effects)
• Transfection