title: A Tmprss2-CreERT2 Knock-In Mouse Model for Cancer Genetic Studies on Prostate and Colon.
abstract: Fusion between TMPRSS2 and ERG, placing ERG under the control of the TMPRSS2 promoter, is the most frequent genetic alteration in prostate cancer, present in 40-50% of cases. The fusion event is an early, if not initiating, event in prostate cancer, implicating the TMPRSS2-positive prostate epithelial cell as the cancer cell of origin in fusion-positive prostate cancer. To introduce genetic alterations into Tmprss2-positive cells in mice in a temporal-specific manner, we generated a Tmprss2-CreERT2 knock-in mouse. We found robust tamoxifen-dependent Cre activation in the prostate luminal cells but not basal epithelial cells, as well as epithelial cells of the bladder and gastrointestinal (GI) tract. The knock-in allele on the Tmprss2 locus does not noticeably impact prostate, bladder, or gastrointestinal function. Deletion of Pten in Tmprss2-positive cells of adult mice generated neoplasia only in the prostate, while deletion of Apc in these cells generated neoplasia only in the GI tract. These results suggest that this new Tmprss2-CreERT2 mouse model will be a useful resource for genetic studies on prostate and colon.
authors.affiliation: Key Laboratory of Systems Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.|Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065, United States of America.
authors.forename: Dong
authors.identifier: http://orcid.org/0000-0003-1821-2741
authors.initials: D
authors.lastname: Gao
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065, United States of America.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Di
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065, United States of America.|Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, New York, United States of America.
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Moore
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065, United States of America.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Sher
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065, United States of America.
authors.forename: Youxin
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065, United States of America.
authors.forename: Shangqian
authors.initials: S
authors.lastname: Wang
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065, United States of America.
authors.forename: Zeda
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065, United States of America.
authors.forename: Devan A
authors.initials: DA
authors.lastname: Murphy
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065, United States of America.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Sawyers
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065, United States of America.|Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065, United States of America.|Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, New York, 10065, United States of America.
authors.forename: Ping
authors.initials: P
authors.lastname: Chi
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065, United States of America.|Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York, 10065, United States of America.|Department of Medicine, Weill Cornell Medical College and New York-Presbyterian Hospital, New York, New York, 10065, United States of America.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D019677:Artificial Gene Fusion / Q000379:methods; D003110:Colonic Neoplasms / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D055879:Gene Knock-In Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D013629:Tamoxifen; D012697:Serine Endopeptidases; C000588699:TMPRSS2 protein, mouse