A new transgenic mouse model for conditional overexpression of the Polycomb Group protein EZH2

The Polycomb Group protein EZH2 is upregulated in most prostate cancers, and its overexpression is associated with poor prognosis. Most insights into the functional role of EZH2 in prostate cancer have been gained using cell lines and EZH2 inactivation studies. However, the question remains whether...

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Bibliographic Details
Published in:Transgenic research Vol. 26; no. 2; pp. 187 - 196
Main Authors: Koppens, Martijn A. J., Tanger, Ellen, Nacerddine, Karim, Westerman, Bart, Song, Ji-Ying, van Lohuizen, Maarten
Format: Journal Article
Language:English
Published: Cham Springer International Publishing 01.04.2017
Springer Nature B.V
Subjects:
Animal Genetics and Genomics
animal models
Animals
bioluminescence
Biomedical and Life Sciences
Biomedical Engineering/Biotechnology
carcinogenesis
crossing
Disease Models, Animal
Enhancer of Zeste Homolog 2 Protein - biosynthesis
Enhancer of Zeste Homolog 2 Protein - genetics
Gene Expression Regulation - genetics
Gene Expression Regulation, Neoplastic
gene overexpression
Genetic Engineering
Humans
image analysis
Life Sciences
luciferase
Male
metastasis
Mice
Mice, Transgenic
Molecular Medicine
monitoring
open reading frames
Original Paper
Plant Genetics and Genomics
Polycomb Repressive Complex 1 - genetics
prognosis
prostatic neoplasms
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Proto-Oncogene Proteins - genetics
PTEN Phosphohydrolase - genetics
tissues
transcription (genetics)
transgenes
transgenic animals
Transgenics
Polycomb
Mouse model
Prostate cancer
EZH2
ISSN:0962-8819, 1573-9368
Online Access:Get full text
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Summary:The Polycomb Group protein EZH2 is upregulated in most prostate cancers, and its overexpression is associated with poor prognosis. Most insights into the functional role of EZH2 in prostate cancer have been gained using cell lines and EZH2 inactivation studies. However, the question remains whether overexpression of EZH2 can initiate prostate tumourigenesis or drive tumour progression. Appropriate transgenic mouse models that are required to answer such questions are lacking. We developed one such transgenic mouse model for conditional overexpression of Ezh2 . In this transgene, Ezh2 and Luciferase are transcribed from a single open reading frame. The latter gene enables intravital bioluminescent imaging of tissues expressing this transgene, allowing the detection of tumour outgrowth and potential metastatic progression over time. Prostate-specific Ezh2 overexpression by crossbreeding with Probasin - Cre mice led to neoplastic prostate lesions at low incidence and with a long latency. Compounding a previously described Bmi1 -transgene and Pten -deficiency prostate cancer mouse model with the Ezh2 transgene did not enhance tumour progression or drive metastasis formation. In conclusion, we here report the generation of a wildtype Ezh2 overexpression mouse model that allows for intravital surveillance of tissues with activated transgene. This model will be an invaluable tool for further unravelling the role of EZH2 in cancer.
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ISSN:0962-8819
1573-9368
DOI:10.1007/s11248-016-9993-x