1. ¹Division of BioMedical Sciences, Faculty of Medicine, Terry Fox Cancer Research Laboratories, Memorial University of Newfoundland, St John's, NL A1B 3V6, Canada
2. ²Department of Pathology and Laboratory Medicine, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL A1B 3V6, Canada

Correspondence: Dr LL Gillespie, E-mail: lgillesp@mun.ca

Received 22 April 2008; Revised 24 June 2008; Accepted 24 June 2008; Published online 29 July 2008.

Abstract

The oestrogen receptor- (ER) plays a key role in breast development and tumorigenesis and inhibiting its activity remains a prime strategy in the treatment of ER-positive breast cancers. Thus, elucidation of the molecular mechanisms responsible for regulating ER activity may facilitate the design of new, more effective breast cancer therapies. The MI-ER1 is a novel transcriptional repressor that contains an LXXLL motif for interaction with nuclear hormone receptors. We investigated the ability of MI-ER1 to bind to ER in HEK293 and MCF-7 breast carcinoma cells, using co-immunoprecipitation assays. In both cell lines, MI-ER1 interacted with ER in the presence and absence of oestrogen, but the interaction was stronger in the absence of ligand. Functional analysis revealed that overexpression of MI-ER1 in T47D breast carcinoma cells results in inhibition of oestrogen-stimulated anchorage-independent growth, suggesting that MI-ER1 may play a role in regulating breast carcinoma cell proliferation in vivo. To explore this further, we performed an immunohistochemical analysis of normal breast tissue and breast carcinoma; a total of 110 cases were examined in whole tissue sections and 771 cases were analysed in tissue microarrays. No consistent difference in the MI-ER1 expression level between normal breast tissue and breast carcinoma was discernible. However, there was a dramatic shift in the subcellular localisation: nuclear MI-ER1 was detectable in 75% of normal breast samples and in 77% of hyperplasia, but in breast carcinoma, only 51% of DCIS, 25% of ILC and 4% of IDC contained nuclear staining. This shift from nuclear to cytoplasmic localisation of MI-ER1 during breast cancer progression suggests that loss of nuclear MI-ER1 might contribute to the development of invasive breast carcinoma.