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用于小鼠前列腺组合荧光标记的新型体内模型。

Novel In Vivo model for combinatorial fluorescence labeling in mouse prostate.

作者信息

Fang Xiaolan, Gyabaah Kenneth, Nickkholgh Bita, Cline J Mark, Balaji K C

机构信息

Department of Cancer Biology, Comprehensive Cancer Center, Wake Forest University Health Sciences, Winston-Salem, North Carolina; Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina.

出版信息

Prostate. 2015 Jun 15;75(9):988-1000. doi: 10.1002/pros.22984. Epub 2015 Mar 8.

Abstract

BACKGROUND

The epithelial layer of prostate glands contains several types of cells, including luminal and basal cells. Yet there is paucity of animal models to study the cellular origin of normal or neoplastic development in the prostate to facilitate the treatment of heterogenous prostate diseases by targeting individual cell lineages.

METHODS

We developed a mouse model that expresses different types of fluorescent proteins (XFPs) specifically in prostatic cells. Using an in vivo stochastic fluorescent protein combinatorial strategy, XFP signals were expressed specifically in prostate of Protein Kinase D1 (PKD1) knock-out, K-Ras(G) (12) (D) knock-in, and Phosphatase and tensin homolog (PTEN) and PKD1 double knock-out mice under the control of PB-Cre promoter.

RESULTS

In vivo XFP signals were observed in prostate of PKD1 knock-out, K-Ras(G) (12) (D) knock-in, and PTEN PKD1 double knock-out mice, which developed normal, hyperplastic, and neoplastic prostate, respectively. The patchy expression pattern of XFPs in neoplasia tissue indicated the clonal origin of cancer cells in the prostate.

CONCLUSIONS

The transgenic mouse models demonstrate combinatorial fluorescent protein expression in normal and cancerous prostatic tissues. This novel prostate-specific fluorescent labeled mouse model, which we named Prorainbow, could be useful in studying benign and malignant pathology of prostate.

摘要

背景

前列腺的上皮层包含多种类型的细胞,包括管腔细胞和基底细胞。然而,用于研究前列腺正常或肿瘤性发育的细胞起源以通过靶向单个细胞谱系来促进异质性前列腺疾病治疗的动物模型却很匮乏。

方法

我们构建了一种小鼠模型,该模型在前列腺细胞中特异性表达不同类型的荧光蛋白(XFPs)。利用体内随机荧光蛋白组合策略,在PB-Cre启动子的控制下,XFP信号在蛋白激酶D1(PKD1)敲除、K-Ras(G)(12)(D)敲入以及磷酸酶和张力蛋白同源物(PTEN)与PKD1双敲除小鼠的前列腺中特异性表达。

结果

在PKD1敲除、K-Ras(G)(12)(D)敲入以及PTEN-PKD1双敲除小鼠的前列腺中观察到体内XFP信号,这些小鼠分别发育出正常、增生性和肿瘤性前列腺。肿瘤组织中XFP的斑驳表达模式表明前列腺癌细胞的克隆起源。

结论

转基因小鼠模型展示了正常和癌性前列腺组织中的组合荧光蛋白表达。这种我们命名为Prorainbow的新型前列腺特异性荧光标记小鼠模型可能有助于研究前列腺的良性和恶性病理学。

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1
Luminal cells are favored as the cell of origin for prostate cancer.管腔细胞被认为是前列腺癌的起源细胞。
Cell Rep. 2014 Sep 11;8(5):1339-46. doi: 10.1016/j.celrep.2014.08.002. Epub 2014 Aug 28.
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Tracking the clonal origin of lethal prostate cancer.追踪致命性前列腺癌的克隆起源。
J Clin Invest. 2013 Nov;123(11):4918-22. doi: 10.1172/JCI70354. Epub 2013 Oct 25.

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