Hakai acts as a coregulator of estrogen receptor alpha in breast cancer cells.

Estrogen receptors play a key role in breast cancer development. One of the current therapeutic strategies for the treatment of estrogen receptor (ER)-α-positive breast cancers relies on the blockade of ERα transcriptional activity. In the present study, we characterized Hakai, originally characterized as an E-cadherin binding protein, as a strong ...
blockade of ERα in breast cancer cells. We showed that Hakai inhibited the transcriptional activity of ERα by binding directly to ERα. The DNA-binding domain of ERα was found to be responsible for its interaction with Hakai. Hakai competed with ERα coactivators, such as steroid receptor coactivator-1 (SRC-1) and glucocoriticord receptor interacting protein-1 (GRIP-1), for the modulation of ERα transactivation, while its ubiquitin-ligase activity was not required. Further, overexpression of Hakai inhibited the proliferation and migration of breast cancer cells. Taken together, these results suggest that Hakai is a novel corepressor of ERα and may play a negative role in the development and progression of breast cancers.
Mesh Terms:
Animals, Binding, Competitive, Blotting, Western, Breast Neoplasms, COS Cells, Cell Line, Tumor, Cell Movement, Cell Proliferation, Cercopithecus aethiops, Estradiol, Estrogen Receptor alpha, Female, Humans, Immunoprecipitation, Nuclear Receptor Coactivator 2, Nuclear Receptor Coactivator 3, Nuclear Receptor Coactivators, Protein Binding, Testosterone, Transcriptional Activation, Transfection, Two-Hybrid System Techniques, Ubiquitin-Protein Ligases
Cancer Sci.
Date: Sep. 01, 2010
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