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.
Terry Fox Cancer Research Laboratories, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, A1B 3V6, Canada. s.li@mun.ca.
Shengnan
S
Li
Terry Fox Cancer Research Laboratories, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, A1B 3V6, Canada. gpaterno@mun.ca.
Gary D
GD
Paterno
Terry Fox Cancer Research Laboratories, Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, A1B 3V6, Canada. lgillesp@mun.ca.
Laura L
LL
Gillespie
D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D061986:MCF-7 Cells; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D021381:Protein Transport; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D007328:Insulin; C470480:MIER1 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; C110550:HDAC1 protein, human; C533423:HDAC2 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2