Reference SummaryPatel SJ, PLoS One 2013;8(4):e61848

Title

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

Authors

 Patel SJ; Molinolo AA; Gutkind S; Crawford NP

Journal

 PLoS One

Volume

 8

Issue

 4

Year

 2013

Pages

 e61848

Abstract

 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.

Links

 J:200102 – MGI References
23620793 – National Library of Medicine/PubMed

Strain Notes

Strain Note
(C57BL/6J x 129S1/SvImJ)F1-Tg(TRAMP)8247Ng These mice were generated by crossing C57BL/6-Tg(TRAMP)8247Ng/J female mice with 129S1/SvImJ male mice, both obtained from the Jackson Laboratory.
(C57BL/6J x A/J)F1-Tg(TRAMP)8247Ng These mice were generated by crossing C57BL/6-Tg(TRAMP)8247Ng/J female mice with A/J male mice, both obtained from the Jackson Laboratory.
(C57BL/6J x CAST/EiJ)F1-Tg(TRAMP)8247Ng These mice were generated by crossing C57BL/6-Tg(TRAMP)8247Ng/J female mice with CAST/EiJ male mice, both obtained from the Jackson Laboratory.
(C57BL/6J x NOD/LtJ)F1-Tg(TRAMP)8247Ng These mice were generated by crossing C57BL/6-Tg(TRAMP)8247Ng/J female mice with NOD/LtJ male mice, both obtained from the Jackson Laboratory.
(C57BL/6J x NZO/HlLtJ)F1-Tg(TRAMP)8247Ng These mice were generated by crossing C57BL/6-Tg(TRAMP)8247Ng/J female mice with NZO/HlLtJ male mice, both obtained from the Jackson Laboratory.
(C57BL/6J x PWK/PhJ)F1-Tg(TRAMP)8247Ng These mice were generated by crossing C57BL/6-Tg(TRAMP)8247Ng/J female mice with PWK/PhJ male mice, both obtained from the Jackson Laboratory.
(C57BL/6J x WSB/EiJ)F1-Tg(TRAMP)8247Ng These mice were generated by crossing C57BL/6-Tg(TRAMP)8247Ng/J female mice with WSB/EiJ male mice, both obtained from the Jackson Laboratory.
C57BL/6-Tg(TRAMP)8247Ng/J These mice were maintained by crossing C57BL/6-Tg(TRAMP)8247Ng/J female mice with C57BL/6J male mice, both obtained from the Jackson Laboratory.
Visual Summary Grid

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6-Tg(TRAMP)8247Ng/J Prostate gland - Anterior lobe hyperplasia Prostate gland - Anterior lobe

observed
(C57BL/6J x NOD/LtJ)F1-Tg(TRAMP)8247Ng Prostate gland - Anterior lobe hyperplasia Prostate gland - Anterior lobe

observed
(C57BL/6J x PWK/PhJ)F1-Tg(TRAMP)8247Ng Prostate gland - Anterior lobe hyperplasia Prostate gland - Anterior lobe

observed
(C57BL/6J x WSB/EiJ)F1-Tg(TRAMP)8247Ng Prostate gland - Anterior lobe hyperplasia Prostate gland - Anterior lobe

observed
C57BL/6-Tg(TRAMP)8247Ng/J Prostate gland - Dorsolateral lobe hyperplasia Prostate gland - Dorsolateral lobe

observed
(C57BL/6J x NOD/LtJ)F1-Tg(TRAMP)8247Ng Prostate gland - Dorsolateral lobe hyperplasia Prostate gland - Dorsolateral lobe

observed
(C57BL/6J x PWK/PhJ)F1-Tg(TRAMP)8247Ng Prostate gland - Dorsolateral lobe hyperplasia Prostate gland - Dorsolateral lobe

observed
(C57BL/6J x WSB/EiJ)F1-Tg(TRAMP)8247Ng Prostate gland - Dorsolateral lobe hyperplasia Prostate gland - Dorsolateral lobe

observed
C57BL/6-Tg(TRAMP)8247Ng/J Prostate gland carcinoma - neuroendocrine Prostate gland

0 - 64
(C57BL/6J x A/J)F1-Tg(TRAMP)8247Ng Prostate gland carcinoma - neuroendocrine Prostate gland

69
(C57BL/6J x 129S1/SvImJ)F1-Tg(TRAMP)8247Ng Prostate gland carcinoma - neuroendocrine Prostate gland

40
(C57BL/6J x NOD/LtJ)F1-Tg(TRAMP)8247Ng Prostate gland carcinoma - neuroendocrine Prostate gland

33 - 100
(C57BL/6J x NZO/HlLtJ)F1-Tg(TRAMP)8247Ng Prostate gland carcinoma - neuroendocrine Prostate gland

70
(C57BL/6J x CAST/EiJ)F1-Tg(TRAMP)8247Ng Prostate gland carcinoma - neuroendocrine Prostate gland

71
(C57BL/6J x PWK/PhJ)F1-Tg(TRAMP)8247Ng Prostate gland carcinoma - neuroendocrine Prostate gland

0 - 25
(C57BL/6J x WSB/EiJ)F1-Tg(TRAMP)8247Ng Prostate gland carcinoma - neuroendocrine Prostate gland

0 - 43
C57BL/6-Tg(TRAMP)8247Ng/J Prostate gland hyperplasia Prostate gland

100
(C57BL/6J x NOD/LtJ)F1-Tg(TRAMP)8247Ng Prostate gland hyperplasia Prostate gland

33 - 100
(C57BL/6J x PWK/PhJ)F1-Tg(TRAMP)8247Ng Prostate gland hyperplasia Prostate gland

67 - 100
(C57BL/6J x WSB/EiJ)F1-Tg(TRAMP)8247Ng Prostate gland hyperplasia Prostate gland

33 - 100
C57BL/6-Tg(TRAMP)8247Ng/J Prostate gland prostatic intraepithelial neoplasia (PIN) Prostate gland

100
(C57BL/6J x NOD/LtJ)F1-Tg(TRAMP)8247Ng Prostate gland prostatic intraepithelial neoplasia (PIN) Prostate gland

33 - 100
(C57BL/6J x PWK/PhJ)F1-Tg(TRAMP)8247Ng Prostate gland prostatic intraepithelial neoplasia (PIN) Prostate gland

67 - 100
(C57BL/6J x WSB/EiJ)F1-Tg(TRAMP)8247Ng Prostate gland prostatic intraepithelial neoplasia (PIN) Prostate gland

33 - 100
C57BL/6-Tg(TRAMP)8247Ng/J Seminal vesicle hyperplasia Seminal vesicle

0 - 100
(C57BL/6J x NOD/LtJ)F1-Tg(TRAMP)8247Ng Seminal vesicle hyperplasia Seminal vesicle

0 - 33
(C57BL/6J x PWK/PhJ)F1-Tg(TRAMP)8247Ng Seminal vesicle hyperplasia Seminal vesicle

0 - 100
(C57BL/6J x WSB/EiJ)F1-Tg(TRAMP)8247Ng Seminal vesicle hyperplasia Seminal vesicle

0 - 100
C57BL/6-Tg(TRAMP)8247Ng/J Seminal vesicle tumor Seminal vesicle

observed
(C57BL/6J x A/J)F1-Tg(TRAMP)8247Ng Seminal vesicle tumor Seminal vesicle

observed
(C57BL/6J x 129S1/SvImJ)F1-Tg(TRAMP)8247Ng Seminal vesicle tumor Seminal vesicle

observed
(C57BL/6J x NOD/LtJ)F1-Tg(TRAMP)8247Ng Seminal vesicle tumor Seminal vesicle

observed
(C57BL/6J x NZO/HlLtJ)F1-Tg(TRAMP)8247Ng Seminal vesicle tumor Seminal vesicle

observed
(C57BL/6J x CAST/EiJ)F1-Tg(TRAMP)8247Ng Seminal vesicle tumor Seminal vesicle

observed
(C57BL/6J x PWK/PhJ)F1-Tg(TRAMP)8247Ng Seminal vesicle tumor Seminal vesicle

observed
(C57BL/6J x WSB/EiJ)F1-Tg(TRAMP)8247Ng Seminal vesicle tumor Seminal vesicle

observed
(C57BL/6J x PWK/PhJ)F1-Tg(TRAMP)8247Ng Seminal vesicle tumor - phyllodes-like Seminal vesicle

50