Insulin and IGF-1, but not 17β-estradiol, alter the subcellular localization of MIER1α in MCF7 breast carcinoma cells.

Background: MIER1α is a transcriptional regulator that interacts with estrogen receptor α and inhibits estrogen-stimulated growth of breast carcinoma cells. Interestingly, analysis of MIER1α subcellular localization in breast samples revealed a stepwise shift from the nucleus to the cytoplasm during progression to invasive carcinoma. Previously, we demonstrated that MIER1α is nuclear in MCF7 cells yet it does not contain a nuclear localization signal. Instead MIER1α is targeted to the nucleus through interaction and co-transport with HDAC 1 and 2.

Results: In this study, we demonstrate that treatment of MCF7 breast carcinoma cells with either insulin or insulin-like growth factor affects the subcellular localization of MIER1α. Both factors reduce the percentage of cells with nuclear MIER1α from 81 and 89 to 41 and 56%, respectively. Treatment with 17β-estradiol, on the other hand, had no effect and MIER1α remained nuclear.

Conclusions: Our data demonstrate that insulin and IGF-1 can contribute to loss of nuclear MIER1α in the MCF7 breast carcinoma cell line.