FKBPL regulates estrogen receptor signaling and determines response to endocrine therapy

Hayley D. McKeen, Christopher Byrne, Puthen V. Jithesh, Christopher Donley, Andrea Valentine, Anita Yakkundi, Martin O'Rourke, Charles Swanton, Helen O. McCarthy, David G. Hirst, Tracy Robson

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The HSP90 chaperone and immunophilin FKBPL is an estrogen-responsive gene that interacts with estogen receptor α (ERα) and regulates its levels. In this study, we explored the effects of FKBPL on breast cancer proliferation. Breast cancer cells stably overexpressing FKBPL became dependent on estrogen for their growth and were dramatically more sensitive to the antiestrogens tamoxifen and fulvestrant, whereas FKBPL knockdown reverses this phenotype. FKBPL knockdown also decreased the levels of the cell cycle inhibitor p21WAF1 and increased ERα phosphorylation on Ser118 in response to 17β-estradiol and tamoxifen. In support of the likelihood that these effects explained FKBPL-mediated cell growth inhibition and sensitivity to endocrine therapies, FKBPL expression was correlated with increased overall survival and distant metastasis-free survival in breast cancer patients. Our findings suggest that FKBPL may have prognostic value based on its impact on tumor proliferative capacity and sensitivity to endocrine therapies, which improve outcome.

Original languageEnglish
Pages (from-to)1090-1100
Number of pages11
JournalCancer Research
Volume70
Issue number3
DOIs
Publication statusPublished - 1 Feb 2010
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

McKeen, H. D., Byrne, C., Jithesh, P. V., Donley, C., Valentine, A., Yakkundi, A., O'Rourke, M., Swanton, C., McCarthy, H. O., Hirst, D. G., & Robson, T. (2010). FKBPL regulates estrogen receptor signaling and determines response to endocrine therapy. Cancer Research, 70(3), 1090-1100. https://doi.org/10.1158/0008-5472.CAN-09-2515