Estrogen receptor α (ERα) is a
transcription factor that induces cell proliferation and exhibits increased expression in a large subset of breast
cancers. The molecular mechanisms underlying the up-regulation of ERα activity, however, remain poorly understood. We identified
FK506-binding protein 52 (
FKBP52) as
a factor associated with poor prognosis of individuals with ERα-positive
breast cancer. We found that
FKBP52 interacts with
breast cancer susceptibility gene 1 and stabilizes ERα, and is essential for
breast cancer cell proliferation.
FKBP52 depletion resulted in decreased ERα expression and proliferation in
breast cancer cell lines, including MCF7-derived
fulvestrant resistance (MFR) cells, suggesting that inhibiting
FKBP52 may provide a
therapeutic effect for endocrine therapy–resistant
breast cancer. In contrast, FKBP51, a closely related molecule to
FKBP52, reduced the stability of ERα. Consistent with these findings, FKBP51 was more abundantly expressed in normal tissues than in
cancer cells, suggesting that these FKBPs may function in the opposite direction. Collectively, our study shows that
FKBP52 and FKBP51 regulate ERα stability in a reciprocal manner and reveals a regulatory mechanism by which the expression of ERα is controlled.