Open AccessHakai acts as a coregulator of estrogen receptor alpha in breast cancer cells
Author(s) -
Gong EunYeung,
Park Eunsook,
Lee Keesook
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01636.x
Subject(s) - transactivation , corepressor , coactivator , estrogen receptor alpha , estrogen receptor , breast cancer , cancer research , estrogen receptor beta , ubiquitin ligase , receptor , nuclear receptor coactivator 1 , nuclear receptor , medicine , endocrinology , biology , cancer , ubiquitin , transcription factor , biochemistry , gene
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. ( Cancer Sci 2010)