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-7SX13) 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-7SX13 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.
Highlights
All tissues and cells respond simultaneously to multiple growth and differentiation factors that influence their development, growth, and differentiation
Our present study showed insulin-like growth factor-I (IGF-I) and its receptor affected the association of insulin-like growth factors (IGF)-IR with ERa, and ERa is involved in IGF-IR signaling pathway induced by IGF-I
We found the association of IGF-IR with ERa was enhanced rapidly after IGF-I or E2 treatment in NWTB3 cells overexpressing IGF-IR and transiently transfected with an exogenous ERa expression plasmid
Summary
All tissues and cells respond simultaneously to multiple growth and differentiation factors that influence their development, growth, and differentiation. Many of these factors are extracellular signaling molecules that reach the cells via the circulation or from local paracrine sources. To influence the biological responses of the cells, these factors or ligands must interact with receptors that signal the intracellular events, culminating in a biological response. Since cells respond to multiple signaling molecules simultaneously, it has recently become of major interest to examine the responses of various cells to receptor activation from multiple classes, rather than studying a single ligand-receptor response in isolation [5]
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