A New Three-Dimensional Ultrasound Microimaging Technology for Preclinical Studies Using a Transgenic Prostate Cancer Mouse Model

Wirtzfeld, Lauren A.; Wu, Guojun; Bygrave, Michael; Yamasaki, Yasuto; Sakai, Hideki; Moussa, Madeleine; Izawa, Jonathan I.; Downey, Dónal B.; Greenberg, Norman M.; Fenster, Aaron; Xuan, Jim W.; Lacefield, James C.

doi:10.1158/0008-5472.can-05-0414

Cited by 83 publications

(74 citation statements)

References 21 publications

(33 reference statements)

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“…Only visible tumor samples of both KIMAP and TGMAP from late-stage prostate cancer were tested. TGMAP tumor tissue (prostate tumor weight, 2-15 g/mouse) was collected showing the majority of androgen-independent and neuroendocrine carcinoma (4,5,23,24). Diploid control tissue samples were from normal spleen cells or peripheral blood leukocytes ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The fast-growing transgenic prostate cancers (PSP-TGMAP), all with palpable tumors with androgenindependent and neuroendocrine features (average, 3-15 g/35 g of body weight), were used as advanced prostate cancer, the most differentiated genes being neuroendocrine-related genes as we have reported (5,24). Prostate cancer tissue from the KIMAP model revealed features of slow-growing and moderately differentiated (androgen dependent) prostate cancer.…”

Section: Resultsmentioning

confidence: 99%

“…All animal experiments were conducted according to standard protocols approved by the University of Western Ontario Council on Animal Care. Procedures of genotyping, transgenic and knock-in mice breeding, anatomic dissection, and pathologic and histologic grading were all done as previously reported (4,5,23,24).…”

Section: Discussionmentioning

confidence: 99%

“…36,46), antimouse Bub1 (monoclonal, 1:1,000; Chemicon, Temecula, CA), and anti-h-actin (polyclonal, 1:2,000; Sigma). Standard SDS-PAGE and Western blotting procedures were followed as previously reported (4,5). Briefly, PC-3 and HeLa cells and tissues were lysed in lysis buffer [50 mmol/L Tris/HCl (pH 7.8), 150 mmol/L NaCl, 1.0% Triton X-100, 1 mmol/L EDTA, 1 mmol/L EGTA, 1 mmol/L phenylmethylsulfonyl fluoride, 2 mmol/L Na 3 VO 4 , 10 mmol/L, h-glycerophosphate, 5 mmol/L Nappi (sodium pyrophosphate)] according to refs.…”

Section: Western Blotting and Immunohistochemistrymentioning

confidence: 99%

“…The SV40 T/t antigen (Tag) oncogene -derived transgenic prostate cancer mouse models, the rat probasin gene -based transgenic adenocarcinoma mouse prostate (TRAMP; refs. [3][4][5] and LPB-SV40 tag (LADY; ref. 6) models, are currently the most prevalent murine prostate cancer model.…”

Section: Introductionmentioning

confidence: 99%

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Bub1 Up-Regulation and Hyperphosphorylation Promote Malignant Transformation in SV40 Tag–Induced Transgenic Mouse Models

Guo

Wu²,

Chin³

et al. 2006

Molecular Cancer Research

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Rodents do not naturally develop prostate cancer. Currently, most widely used genetically engineered mouse prostate cancer models use SV40 T/tag oncogene. To understand the mechanism underlying prostate cancer development in transgenic and knock-in SV40 Tag mouse models, we did cDNA microarray analyses, comparing gene expression profiles of prostate cancer tissues from early-, late-, and advance-stage androgen-independent prostate cancers. Of the 67 genes that were up-regulated by z10-fold, 40 are known to be required for chromosome stability. In particular, the spindle checkpoint component Bub1 was persistently up-regulated from early to advanced androgen-independent prostate cancer lesions. Significantly, Bub1, which is required for accurate chromosome segregation during mitosis, has recently been reported to bind SV40 Tag. Consistent with a spindle checkpoint defect, flow cytometry experiments indicate that advanced androgen-independent prostate cancer tumors exhibit aneuploidy, along with up-regulation of levels of both Bub1 mRNA and Bub1 protein or hyperphosphorylation. Importantly, up-regulation and hyperphosphorylation of Bub1 were also observed in established human prostate cancer cell lines and in clinical studies. Furthermore, analysis of human prostate cancer lines showed impaired spindle checkpoint function and endoreduplication following exposure to spindle toxins. Small interfering RNA -mediated repression of Bub1 in the human prostate cancer line PC-3 restrained cell proliferation, an effect mimicked by inhibition of mitogen-activated protein kinase, an upstream activator of Bub1. Thus, by perturbing Bub1 function, our observations suggest a new mechanism whereby the SV40 Tag oncoprotein promotes chromosomal instability and aneuploidy in transgenic mouse prostate cancer models. Whereas the exact details of this mechanism remain unclear, our novel findings raise the possibility of exploiting Bub1 as a new therapeutic target in the treatment of prostate cancer, the most common cancer in adult men in North America. (Mol Cancer Res 2006;4(12):957 -69)

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Western Blotting and Immunohistochemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Bub1 Up-Regulation and Hyperphosphorylation Promote Malignant Transformation in SV40 Tag–Induced Transgenic Mouse Models

Guo

Wu²,

Chin³

et al. 2006

Molecular Cancer Research

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Ultrasound Imaging in Live Animals

Faita

2019

Handbook of in Vivo Chemistry in Mice

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Detection of different tumor growth kinetics in single transgenic mice with oncogene‐induced mammary carcinomas by flat‐panel volume computed tomography

Jannasch

Dullin

Heinlein

et al. 2009

Intl Journal of Cancer

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Transgenic mouse models offer an excellent opportunity for studying the molecular basis of cancer development and progression. Here we applied flat-panel volume computed tomography (fpVCT) to monitor tumor progression as well as the development of tumor vasculature in vivo in a transgenic mouse model for oncogene-induced mammary carcinogenesis (WAP-T mice). WAP-T mice develop multiple mammary carcinomas on oncogene induction within 3 to 5 months. Following induction, 3-dimensional fpVCT data sets were obtained by serial single scans of entire mice in combination with iodine containing contrast agents and served as basis for precise measurements of tumor volumes. Thereby, we were able to depict tumors within the mammary glands at a very early stage of the development. Tumors of small sizes (0.001 cm 3 ) were detected by fpVCT before being palpable or visible by inspection. The capability to determine early tumor onset combined with longitudinal noninvasive imaging identified diverse time points of tumor onset for each mammary carcinoma and different tumor growth kinetics for multiple breast carcinomas that developed in single mice. Furthermore, blood supply to the breast tumors, as well as blood vessels around and within the tumors, were clearly visible over time by fpVCT. Three-dimensional visualization of tumor vessels in high resolution was enhanced by the use of a novel blood pool contrast agent. Here, we demonstrate by longitudinal fpVCT imaging that mammary carcinomas develop at different time points in each WAP-T mouse, and thereafter show divergent growth rates and distinct vascularization patterns. ' UICCKey words: flat-panel volume computed tomography; in vivo imaging; murine transgenic tumor models; tumor angiogenesis Accompanying the rapid progress in deciphering the human and mouse genome, many transgenic mouse models have been generated. Weissleder and Mahmood already assumed in 2001 that more than 25 million transgenic and knockout mice would be raised that year for experimental studies, accounting for over 90% of all mammals in research.1 These mouse models offer the opportunity to study gene functions in their biological context in a much more physiological way than any other approach. Especially cancer research benefits from the advantages of these transgenic mice in elucidating the role of a specific gene in tumor growth and spread as well as angiogenesis. One promising model in addressing such questions is the WAP-T transgenic mouse. [2][3][4] In these mice, the SV40 early gene region is induced specifically in differentiating mammary epithelial cells upon activation of the WAPpromoter during late pregnancy and lactation, and drives mammary carcinogenesis in mammary epithelial cells re-expressing the transgene after involution of the mammary glands. The SV40 early region mainly serves to functionally eliminate the p53 and pRb tumor suppressors by binding to the SV40 large T-antigen 5 and to change the specificity of the phosphatase PP2A 6 by its interaction with SV40 small T-antigen, thereby...

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A New Three-Dimensional Ultrasound Microimaging Technology for Preclinical Studies Using a Transgenic Prostate Cancer Mouse Model

Cited by 83 publications

References 21 publications

Bub1 Up-Regulation and Hyperphosphorylation Promote Malignant Transformation in SV40 Tag–Induced Transgenic Mouse Models

Bub1 Up-Regulation and Hyperphosphorylation Promote Malignant Transformation in SV40 Tag–Induced Transgenic Mouse Models

Ultrasound Imaging in Live Animals

Detection of different tumor growth kinetics in single transgenic mice with oncogene‐induced mammary carcinomas by flat‐panel volume computed tomography

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