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pubmed:abstractText |
Estrogen receptors play a key role in breast cancer development. One of the current therapeutic strategies for the treatment of estrogen receptor (ER)-?-positive breast cancers relies on the blockade of ER? transcriptional activity. In the present study, we characterized Hakai, originally characterized as an E-cadherin binding protein, as a strong blockade of ER? in breast cancer cells. We showed that Hakai inhibited the transcriptional activity of ER? by binding directly to ER?. The DNA-binding domain of ER? was found to be responsible for its interaction with Hakai. Hakai competed with ER? coactivators, such as steroid receptor coactivator-1 (SRC-1) and glucocoriticord receptor interacting protein-1 (GRIP-1), for the modulation of ER? 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 ER? and may play a negative role in the development and progression of breast cancers.
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