Initiation of prostate cancer in mice by Tp53R270H: evidence for an alternative molecular progression.

Disease Models & Mechanisms
Ruth L VinallAlexander D Borowsky

Abstract

Tp53 mutations are common in human prostate cancer (CaP), occurring with a frequency of ∼30% and ∼70% in localized and metastatic disease, respectively. In vitro studies have determined several common mutations of Tp53 that have specific gain-of-function properties in addition to loss of function, including the ability to promote castration-resistant (CR) growth of CaP cells in some contexts. To date, a lack of suitable mouse models has prohibited investigation of the role played by Tp53 mutations in mediating CaP progression in vivo. Here, we describe the effects of conditional expression of a mutant Tp53 (Tp53(R270H); equivalent to the human hotspot mutant R273H) in the prostate epithelium of mice. Heterozygous "Tp53(LSL-R270H/+)" [129S4(Trp53(tm3Tyj))] and "Nkx3.1-Cre" [129S(Nkx3-1(tm3(cre)Mms))] mice with prostate-specific expression of the Tp53(R270H) mutation (p53(R270H/+) Nkx3.1-Cre mice) were bred onto an FVB/N background via speed congenesis to produce strain FVB.129S4(Trp53(tm3Tyj/wt)); FVB.129S(Nkx3-1(tm3(cre)Mms/wt)) and littermate genotype negative control mice. These mutant mice had significantly increased incidences of prostatic intraepithelial neoplasia (PIN) lesions, and these appeared earlier, compared with th...Continue Reading

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Citations

Jan 24, 2014·Cancer Metastasis Reviews·Magdalena M GrabowskaRobert J Matusik
Jul 27, 2015·Cancer Treatment Reviews·Galina KhemlinaRazelle Kurzrock
Oct 26, 2016·Advances in Biological Regulation·James A McCubreyLinda S Steelman
Apr 18, 2018·Cold Spring Harbor Perspectives in Medicine·Juan M Arriaga, Cory Abate-Shen
Jul 17, 2019·Journal of Experimental & Clinical Cancer Research : CR·Monika AggarwalFung-Lung Chung
May 1, 2013·Personalized Medicine·Won Kim, Phillip G Febbo

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Methods Mentioned

BETA
PCR
laser capture microdissection

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