Germline genetic variation modulates tumor progression and metastasis in a mouse model of neuroendocrine prostate carcinoma.

Neuroendocrine (NE) differentiation has gained increased attention as a prostate cancer (PC) prognostic marker. The aim of this study is to determine whether host germline genetic variation influences tumor progression and metastasis in C57BL/6-Tg(TRAMP)8247Ng/J (TRAMP) mouse model of aggressive NEP...

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Autores principales:	Shashank J Patel, Alfredo A Molinolo, Silvio Gutkind, Nigel P S Crawford
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/98df94023eb24663a41da0fd4f7b9870
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spelling	oai:doaj.org-article:98df94023eb24663a41da0fd4f7b98702021-11-18T07:48:42ZGermline genetic variation modulates tumor progression and metastasis in a mouse model of neuroendocrine prostate carcinoma.1932-620310.1371/journal.pone.0061848https://doaj.org/article/98df94023eb24663a41da0fd4f7b98702013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23620793/?tool=EBIhttps://doaj.org/toc/1932-6203Neuroendocrine (NE) differentiation has gained increased attention as a prostate cancer (PC) prognostic marker. The aim of this study is to determine whether host germline genetic variation influences tumor progression and metastasis in C57BL/6-Tg(TRAMP)8247Ng/J (TRAMP) mouse model of aggressive NEPC. TRAMP mice were crossed to the eight progenitor strains of the Collaborative Cross recombinant inbred panel to address this. Tumor growth and metastasis burden were quantified in heterozygous transgene positive F1 male mice at 30 weeks of age. Compared to wild-type C57BL/6J-Tg(TRAMP)824Ng/J males, TRAMP x CAST/EiJ, TRAMP x NOD/ShiLtJ and TRAMP x NZO/HlLtJ F1 males displayed significant increases in tumor growth. Conversely, TRAMP x WSB/EiJ and TRAMP x PWK/PhJ F1 males displayed significant reductions in tumor growth. Interestingly, despite reduced tumor burden, TRAMP x WSB/EiJ males had an increased nodal metastasis burden. Patterns of distant pulmonary metastasis tended to follow the same patterns as that of local dissemination in each of the strains. All tumors and metastases displayed positive staining for NE markers, synaptophysin, and FOXA2. These experiments conclusively demonstrate that the introduction of germline variation by breeding modulates tumor growth, local metastasis burden, and distant metastasis frequency in this model of NEPC. These strains will be useful as model systems to facilitate the identification of germline modifier genes that promote the development of aggressive forms of PC.Shashank J PatelAlfredo A MolinoloSilvio GutkindNigel P S CrawfordPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e61848 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shashank J Patel Alfredo A Molinolo Silvio Gutkind Nigel P S Crawford Germline genetic variation modulates tumor progression and metastasis in a mouse model of neuroendocrine prostate carcinoma.
description	Neuroendocrine (NE) differentiation has gained increased attention as a prostate cancer (PC) prognostic marker. The aim of this study is to determine whether host germline genetic variation influences tumor progression and metastasis in C57BL/6-Tg(TRAMP)8247Ng/J (TRAMP) mouse model of aggressive NEPC. TRAMP mice were crossed to the eight progenitor strains of the Collaborative Cross recombinant inbred panel to address this. Tumor growth and metastasis burden were quantified in heterozygous transgene positive F1 male mice at 30 weeks of age. Compared to wild-type C57BL/6J-Tg(TRAMP)824Ng/J males, TRAMP x CAST/EiJ, TRAMP x NOD/ShiLtJ and TRAMP x NZO/HlLtJ F1 males displayed significant increases in tumor growth. Conversely, TRAMP x WSB/EiJ and TRAMP x PWK/PhJ F1 males displayed significant reductions in tumor growth. Interestingly, despite reduced tumor burden, TRAMP x WSB/EiJ males had an increased nodal metastasis burden. Patterns of distant pulmonary metastasis tended to follow the same patterns as that of local dissemination in each of the strains. All tumors and metastases displayed positive staining for NE markers, synaptophysin, and FOXA2. These experiments conclusively demonstrate that the introduction of germline variation by breeding modulates tumor growth, local metastasis burden, and distant metastasis frequency in this model of NEPC. These strains will be useful as model systems to facilitate the identification of germline modifier genes that promote the development of aggressive forms of PC.
format	article
author	Shashank J Patel Alfredo A Molinolo Silvio Gutkind Nigel P S Crawford
author_facet	Shashank J Patel Alfredo A Molinolo Silvio Gutkind Nigel P S Crawford
author_sort	Shashank J Patel
title	Germline genetic variation modulates tumor progression and metastasis in a mouse model of neuroendocrine prostate carcinoma.
title_short	Germline genetic variation modulates tumor progression and metastasis in a mouse model of neuroendocrine prostate carcinoma.
title_full	Germline genetic variation modulates tumor progression and metastasis in a mouse model of neuroendocrine prostate carcinoma.
title_fullStr	Germline genetic variation modulates tumor progression and metastasis in a mouse model of neuroendocrine prostate carcinoma.
title_full_unstemmed	Germline genetic variation modulates tumor progression and metastasis in a mouse model of neuroendocrine prostate carcinoma.
title_sort	germline genetic variation modulates tumor progression and metastasis in a mouse model of neuroendocrine prostate carcinoma.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/98df94023eb24663a41da0fd4f7b9870
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Germline genetic variation modulates tumor progression and metastasis in a mouse model of neuroendocrine prostate carcinoma.

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