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Intrinsic RB activation induces tumoral and stromal anti-tumor responses that limit triple-negative breast cancer [RNA-Seq]

GSE310025 Homo sapiens; Mus musculus Expression profiling by high throughput sequencing 28 samples Submitted 2025/11/17 Platform GPL24676Platform GPL13112
Summary
The RB tumor suppressor is a key regulator of cell cycle progression that is often inactivated in triple-negative breast cancer (TNBC). Recent studies indicate that drugs activating RB have multiple tumor-suppressing effects on the tumor and the tumor microenvironment (TME). Here, we utilize a constitutively active RB protein incapable of being phosphorylated and inactivated by CDKs (RBΔCDK) to assess the intrinsic sufficiency of RB activation on tumor suppression. Expression of RBΔCDK in TNBC cell lines uniformly inhibited proliferation. Transcriptomic analysis revealed suppression of cell cycle genes and the induction of genes associated with interferon response. Similarly, tumor growth and metastasis were suppressed in RBΔCDK expressing human xenograft and mouse syngeneic tumor models. RB activation was sufficient to dramatically alter the TME, wherein tumor growth suppression was mediated by CD8+ T cells. Together, these data indicate that active RB suppresses TNBC progression in cancer cell-autonomous and non-autonomous mechanisms.
Published in
Intrinsic RB activation induces tumoral and stromal anti-tumor responses that limit triple-negative breast cancer
Wan Y, Wang J, O'Connor TN et al. · NPJ breast cancer 2025 · PMID 41326426 · doi:10.1038/s41523-025-00845-5
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Direct links to NCBI, no account and no request form: the whole study as GSE310025_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 28 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1365018 and SRA study SRP644934. Searching any of these in the dataset finder brings you back here.

Study design
8 conditions, mostly with about 4 replicates each
4T1, Control, ×4 4T1, Dox treated, ×4 HCC1806, Control, ×4 HCC1806, Dox treated, ×4 AT3, Control, ×3 AT3, Dox treated, ×3 MDA-MB-231, Control, ×3 MDA-MB-231, Dox treated, ×2 +1 more

Supports a case/control comparison: 14 samples read as cases, 14 as controls.

8 replicated groups read from 28 sample titles; they account for 27 of them. Check it against the sample list below before relying on it.

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