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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Vydáno v:	Transgenic research Ročník 26; číslo 2; s. 187 - 196
Hlavní autoři:	Koppens, Martijn A. J., Tanger, Ellen, Nacerddine, Karim, Westerman, Bart, Song, Ji-Ying, van Lohuizen, Maarten
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Cham Springer International Publishing 01.04.2017 Springer Nature B.V
Témata:	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
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Abstract	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.
AbstractList	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. 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.
Author	van Lohuizen, Maarten Koppens, Martijn A. J. Tanger, Ellen Westerman, Bart Nacerddine, Karim Song, Ji-Ying
Author_xml	– sequence: 1 givenname: Martijn A. J. surname: Koppens fullname: Koppens, Martijn A. J. organization: Division of Molecular Genetics, H4012, The Netherlands Cancer Institute – sequence: 2 givenname: Ellen surname: Tanger fullname: Tanger, Ellen organization: Division of Molecular Genetics, H4012, The Netherlands Cancer Institute – sequence: 3 givenname: Karim surname: Nacerddine fullname: Nacerddine, Karim organization: Division of Molecular Genetics, H4012, The Netherlands Cancer Institute – sequence: 4 givenname: Bart surname: Westerman fullname: Westerman, Bart organization: Division of Molecular Genetics, H4012, The Netherlands Cancer Institute – sequence: 5 givenname: Ji-Ying surname: Song fullname: Song, Ji-Ying organization: Department of Experimental Animal Pathology, The Netherlands Cancer Institute – sequence: 6 givenname: Maarten surname: van Lohuizen fullname: van Lohuizen, Maarten email: M.V.Lohuizen@NKI.NL organization: Division of Molecular Genetics, H4012, The Netherlands Cancer Institute, Cancer Genomics Centre Netherlands, CGC.nl
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CitedBy_id	crossref_primary_10_1080_14728222_2018_1451839 crossref_primary_10_3389_fphar_2019_00235 crossref_primary_10_1038_s41467_019_13105_5 crossref_primary_10_3390_cells11050909 crossref_primary_10_1016_j_ccell_2018_06_001 crossref_primary_10_1007_s44178_024_00134_4
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Keywords	Polycomb Mouse model Prostate cancer EZH2
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Snippet	The Polycomb Group protein EZH2 is upregulated in most prostate cancers, and its overexpression is associated with poor prognosis. Most insights into the...
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SubjectTerms	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
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Title	A new transgenic mouse model for conditional overexpression of the Polycomb Group protein EZH2
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