Rat somatic genome editing enables ER+ breast cancer modeling
Abstract
Genetically engineered mouse models have advanced cancer research, but they fail to mimic some human diseases. Rats offer a powerful alternative for modeling human cancers that are inadequately represented in mice, yet their use has been constrained by technical barriers to genome editing. Here, we report somatic genome editing in rats and apply this approach to model estrogen receptor (ER)-positive breast cancer, which accounts for approximately 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 microenvironment 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 the rapid generation of clinically relevant rat tumor models, opening avenues to study tumor biology, therapeutic response, and immune interactions in cancer subtypes previously inaccessible to experimental modeling.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (23)
Wen Bu
Lester and Sue Smith Breast Center, Baylor College of Medicine
Tobie D. Lee
Lester and Sue Smith Breast Center, Baylor College of Medicine
Meenakshi Anurag
Lester and Sue Smith Breast Center, Baylor College of Medicine
Yongchao Dou
Lester and Sue Smith Breast Center, Baylor College of Medicine
Yunfeng Ding
Lester and Sue Smith Breast Center, Baylor College of Medicine
Zhiao Shi
Lester and Sue Smith Breast Center, Baylor College of Medicine
Ruixin Xu
Lester and Sue Smith Breast Center, Baylor College of Medicine
Lillian He
Lester and Sue Smith Breast Center, Baylor College of Medicine
Alexandria Z. Bu
Lester and Sue Smith Breast Center, Baylor College of Medicine
Chandandeep Nagi
Department of Pathology, Baylor College of Medicine
Carolina Gutierrez
Lester and Sue Smith Breast Center, Baylor College of Medicine
Jing Wang
Hunan Cancer Hospital Changsha China
Susan G. Hilsenbeck
Lester and Sue Smith Breast Center, Baylor College of Medicine
Chonghui Cheng
Lester and Sue Smith Breast Center, Baylor College of Medicine
Bing Zhang
Shixia Huang
Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine
Jianming Xu
State Key Laboratory of Soil Pollution Control and Safety,
C. Kent Osborne
Lester and Sue Smith Breast Center, Baylor College of Medicine
Arun Sreekumar
Department of Molecular and Cellular Biology, Baylor College of Medicine
Eric C. Chang
Lester and Sue Smith Breast Center, Baylor College of Medicine
Chad J. Creighton
Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine
Xiang H.-F. Zhang
Lester and Sue Smith Breast Center, Baylor College of Medicine
Yi Li