Rat somatic genome editing enables ER+ breast cancer modeling
Bu, W.; Lee, T. K.; Anurag, M.; Ding, Y.; Xu, R.; He, L.; Bu, A. Z.; Nagi, C. K.; Gutierrez, C.; Hilsenbeck, S. K.; Cheng, C.; Zhang, B.; Huang, S.; Xu, J.; Osborne, C. K.; Sreekumar, A.; Chang, E.; Creighton, C. J.; Zhang, X.; Li, Y.
Show abstract
Genetically engineered mouse models have advanced cancer research but often fail to capture key features of certain human tumors. Rats, with distinct physiology and tumor biology, offer a powerful alternative, yet their use has been constrained by technical barriers to genome editing. Here, we report efficient somatic genome editing in rats, enabling both Indel and substitution mutations. We then apply this approach to model estrogen receptor (ER)-positive breast cancer, which accounts for [~]70% of human cases but remains poorly represented in mice. The resulting rat tumors reproduce hallmarks of human ER+ breast cancer, including ductal histology, hormone responsiveness, and immune-microenvironmental features. By contrast, identical genetic alterations in mice failed to yield ER+ tumors, underscoring critical species differences in tumorigenesis. Together, this work establishes a versatile platform for rapid generation of clinically relevant rat tumor models, opening new avenues to dissect tumor biology, therapeutic response, and immune interactions in previously inaccessible cancer subtypes.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Lineage plasticity enables low-ER luminal tumors to evolve and gain basal-like traits 98%
- Integrative multi-omic sequencing reveals the MMTV-Myc mouse model mimics human breast cancer heterogeneity 97%
- Acquired mutations and transcriptional remodeling in long-term estrogen-deprived locoregional breast cancer recurrences 96%
Similar papers in this journal
- Influence of genetic ancestry on breast stromal cells provides biologic basis for increased incidence of metaplastic breast cancer in women of African descent 97%
- C/EBPB-dependent Adaptation to Palmitic Acid Promotes Stemness in Hormone Receptor Negative Breast Cancer 96%
- Mismatch repair deficiency predicts response to HER2 blockade in HER2-negative breast cancer 96%
Similar papers in this journal
- Neoplastic immune mimicry potentiates breast tumor progression 95%
- Modeling High-grade serous ovarian carcinoma using a combination of in vivo electroporation and CRISPR/Cas9 mediated genome editing 95%
- CIP2A interacts with TopBP1 and is selectively essential for DNA damage-induced basal-like breast cancer tumorigenesis 95%
Similar papers in this journal
- The clinical and molecular significance associated with STING signaling in estrogen receptor-positive early breast cancer 95%
- The breast pre-cancer atlas illustrates the molecular and micro-environmental diversity of ductal carcinoma in situ 95%
- Cyclin E1 protein is stabilized in BRCA1 mutated breast cancers leading to synergy between CDK2 and PARP inhibitors 95%
Similar papers in this journal
- Molecular portraits of cell cycle checkpoint kinases in cancer evolution, progression, and treatment responsiveness 95%
- Aneuploidy and deregulated DNA damage response define haploinsufficiency in breast tissues of BRCA2 mutation carriers 95%
- An EMT-primary cilium-GLIS2 signaling axis regulates mammogenesis and claudin-low breast tumorigenesis 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.