scholarly journals In situ CRISPR‐Cas9 base editing for the development of genetically engineered mouse models of breast cancer

2020 ◽  
Vol 39 (5) ◽  
Author(s):  
Stefano Annunziato ◽  
Catrin Lutz ◽  
Linda Henneman ◽  
Jinhyuk Bhin ◽  
Kim Wong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mouse Models ◽  
Genetically Engineered ◽  
Base Editing ◽  
Genetically Engineered Mouse Models

scholarly journals Genetically engineered mouse models of PI3K signaling in breast cancer

2013 ◽  
Vol 7 (2) ◽  
pp. 146-164 ◽  
Author(s):  
Sjoerd Klarenbeek ◽  
Martine H. van Miltenburg ◽  
Jos Jonkers
Keyword(s):  
Breast Cancer ◽  
Mouse Models ◽  
Genetically Engineered ◽  
Pi3k Signaling ◽  
Genetically Engineered Mouse Models

scholarly journals Transcriptomic classification of genetically engineered mouse models of breast cancer identifies human subtype counterparts

2013 ◽  
Vol 14 (11) ◽  
pp. R125 ◽  
Author(s):  
Adam D Pfefferle ◽  
Jason I Herschkowitz ◽  
Jerry Usary ◽  
Joshua Harrell ◽  
Benjamin T Spike ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mouse Models ◽  
Genetically Engineered ◽  
Genetically Engineered Mouse Models

738 Establishment and application of a series of genetically engineered mouse derived breast cancer homograft models

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A783-A783
Author(s):  
Yanrui Song ◽  
Jessie Wang ◽  
Likun Zhang ◽  
Annie An ◽  
Henry Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mouse Models ◽  
Hormone Receptor ◽  
Triple Negative ◽  
T Antigen ◽  
Genetically Engineered ◽  
Her2 Positive ◽  
Genetically Engineered Mouse Models ◽  
Immune Profiling ◽  
Robust Response

BackgroundBreast cancer is a complex disease which is defined by an intrinsic heterogeneity at the histopathological and molecular levels, as well as in response to therapy. It remains the second leading cause of cancer death among women worldwide despite advances in screening, detection and new therapeutic options. Therefore, it is important to establish relevant preclinical mouse models to study new therapeutics and tumor biology. Genetically engineered mouse models (GEMMs) have been developed in order to understand the molecular, biochemical and cellular functions of oncogenes or tumor suppressor genes. However, the application of GEMMs is constrained due to the spontaneous nature of tumor onset and progression and high cost of breeding. Homograft tumor models, which are derived from and retain the histopathological and molecular features of GEMMs, can be used as faithful surrogates of human tumors.MethodsWe generated a series of homograft tumor models from GEMMs overexpressing human epidermal growth factor receptor 2 (HER2, also known as ERBB2) or polyomavirus middle T antigen (PyMT) driven by the mouse mammary tumor virus (MMTV) promoter, or Simian Virus 40 T-antigen (SV40 Tag) under the promotion of the rat prostate steroid binding protein (C3(1)), which are commonly used GEMMs in preclinical breast cancer research.1 2 Models were generated by transplanting the mammary tumors into donor animals. Furthermore, we characterized the homograft tumors through histopathological analysis, immunohistochemical analysis, and immune profiling, as well as immunotherapeutic, cytotoxic and targeted therapy.ResultsNine breast cancer homograft models were developed from MMTV-ERBB2, MMTV-PyMT and C3(1)-Tag GEMMs, including six hormone receptor negative and HER2 positive models (mBR9013, mBR9026, mBR9027, mBR9028, mBR9029, mBR9030), one hormone receptor positive and HER2 negative model (mBR6174) and two triple negative models (mBR6004, mBR9014). Immune profiling of six models showed enriched macrophage infiltration in the tumor microenvironment. Immunotherapy treatment with anti-mPD-1 and anti-mCTLA-4 produced tumor growth inhibition (TGI) of 98% and 110%, respectively, in the triple negative model mBR9014, accompanied by tumor regression. HER2 targeted treatment with lapatinib produced robust response with TGI ranging from 48% to 97% in one HER2 negative and two HER2 positive models. Varying response to the cytotoxic treatments was observed among different models, with cisplatin producing robust response of TGI over 80% in all five of the tested models.ConclusionsWe have generated and characterized a series of mouse breast cancer homograft models from GEMMs to facilitate both mechanistic investigation and preclinical testing of novel therapeutics.Ethics ApprovalAnimal experiments were conducted in accordance with animal welfare law, approved by local authorities, and in accordance with the ethical guidelines of CrownBio (Taicang).ReferencesSakamoto K, Schmidt JW, Wagner K-U. Mouse models of breast cancer. Methods Mol Biol 2015;1267:47–71.Usary J, Darr DB, Pfefferle AD, et al. Overview of genetically engineered mouse models of distinct breast cancer subtypes. Curr Protoc Pharmacol 2016;72:14.38.1–14.38.11.

scholarly journals Assessing estrogen signaling aberrations in breast cancer risk using genetically engineered mouse models

2011 ◽  
Vol 1229 (1) ◽  
pp. 147-155 ◽  
Author(s):  
Priscilla A. Furth ◽  
M. Carla Cabrera ◽  
Edgar S. Díaz-Cruz ◽  
Sarah Millman ◽  
Rebecca E. Nakles
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Mouse Models ◽  
Genetically Engineered ◽  
Estrogen Signaling ◽  
Genetically Engineered Mouse Models
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