FKBP52 and FKBP51 differentially regulate the stability of estrogen receptor in breast cancer

Makoto Habara, Yuki Sato, Takahiro Goshima, Masashi Sakurai, Hiroyuki Imai, Hideyuki Shimizu, Yuta Katayama, Shunsuke Hanaki, Takahiro Masaki, Masahiro Morimoto, Sayaka Nishikawa, Tatsuya Toyama, Midori Shimada

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere2110256119
JournalProceedings of the National Academy of Sciences of the United States of America
Volume119
Issue number15
DOIs
Publication statusPublished - Apr 12 2022

All Science Journal Classification (ASJC) codes

  • General

Fingerprint

Dive into the research topics of 'FKBP52 and FKBP51 differentially regulate the stability of estrogen receptor in breast cancer'. Together they form a unique fingerprint.

Cite this