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Nuclear FGF2, Androgen Receptor and Wnt Pathway Activation Define a Targetable Subset of Antiprogestin-Resistant Luminal Breast Cancer

GSE315149 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2026/04/01 Platform GPL16791
Summary
We used PR+ T47D and T47D‑YA cell lines engineered to overexpress FGF2 to investigate FGF2‑driven antiprogestin resistance. Transcriptome profiling, qRT-PCR, immunohistochemistry, and in vivo assays were performed to assess hormone receptor expression, pathway alterations, and therapeutic response. We evaluated nuclear androgen receptor (AR) and FGF2 in luminal breast cancer specimens. RNA-seq showed that FGF2 overexpression dysregulated Wnt signaling, downregulated estrogen receptor (ER) and PR, and upregulated AR expression. PR isoform B (PRB) predominated over isoform A, consistent with an antiprogestin-resistant phenotype. FGF2-overexpressing xenografts showed antiprogestin resistance, increased proliferation, and lung metastasis. AR and Wnt pathway blockade impaired tumor growth, and combined treatment further reduced tumor and metastatic burden. In clinical samples, nuclear FGF2 correlated with elevated AR levels in ER+PR− and PRB-high tumors.
Published in
Nuclear FGF2, androgen receptor and Wnt pathway activation define a targetable subset of antiprogestin-resistant luminal breast cancer
Figueroa V, Coianis MI, Sahores A et al. · British journal of cancer 2026 · PMID 41935240 · doi:10.1038/s41416-026-03420-2
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Also filed as BioProject PRJNA1395058 and SRA study SRP658630. Searching any of these in the dataset finder brings you back here.

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