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-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.

Insulin-like growth factor-1, growth hormone, and daily cycling estrogen are associated with mammographic density in premenopausal women

“…Altogether, even if plausible mechanisms have been suggested, and has been supported by experimental studies [41], less is known about the association of the GH-IGF signaling pathway, estrogen and mammographic density. Recently, estrogen and IGF-1 have been observed to have synergistic effects on the growth of breast cancer cells [41].…”

“…Recently, estrogen and IGF-1 have been observed to have synergistic effects on the growth of breast cancer cells [41]. Moreover, GH regulates the production of IGF-1, and around 99% of circulating IGF-1 is bound to IGFBP-3.…”

“…Furthermore, percent mammographic density refers to the structure of the adipose, epithelial and connective tissue in the breast [51]. Thus, the growth factors and estrogens in combination, are key factors in proliferation of breast cells and are potential drivers for breast cancer development [41].…”

Expression and Clinical Significance of Sushi Domain-Containing Protein 3 (SUSD3) and Insulin-like Growth Factor-I Receptor (IGF-IR) in Breast Cancer

“…And the test results are consistent with the result of radioimmunoassay and immunocytochemistry (ICC) by other researchers (Surmacz, 2000). The present study also found the expression rate of IGF-IR and SUSD3 in ER-positive breast cancer tissue was significantly higher than that in ER-negative tissue.Our previous studies have shown that IGF-IR has interaction with ER in MCF-7 and NWTB3 breast cancer cell lines, and estrogen can induce the expression IGF-IR (Yu et al, 2013a). However, there is no report about association between SUSD3 and IGF-IR currently.…”

Aloe Emodin Induces Apoptosis in ER+-breast Cancer Cells; MCF-7 through IGF-1R Signalling Pathway

“…The 17β-estradiol-ERα complex binds and activates IGF-1R directly. Vice versa, IGF signalling enhances ERα activation in human breast cancer cells by phosphorylation (Yu et al 2013). 17β-estradiol and IGF-1R synergistically enhances S phase entry in breast tumor cells (Yu et al 2013).…”