Nuclear FGFR1 Regulates Gene Transcription and Promotes Antiestrogen Resistance in ER⁺ Breast Cancer.

ABSTRACT:

Purpose

FGFR1 overexpression has been associated with endocrine resistance in ER⁺ breast cancer. We found FGFR1 localized in the nucleus of breast cancer cells in primary tumors resistant to estrogen suppression. We investigated a role of nuclear FGFR1 on gene transcription and antiestrogen resistance.

Experimental design

Tumors from patients treated with letrozole were subjected to Ki67 and FGFR1 IHC. MCF7 cells were transduced with FGFR1(SP-)(NLS) to promote nuclear FGFR1 overexpression. FGFR1 genomic activity in ER⁺/FGFR1-amplified breast cancer cells ± FOXA1 siRNA or ± the FGFR tyrosine kinase inhibitor (TKI) erdafitinib was examined by chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq). The nuclear and chromatin

SUBMITTER: Servetto A 

PROVIDER: S-EPMC8338892 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature