Study of the Protooncogene Wnt-1 Induced Mammary Hyperplasias in Wn-1 Transgenic Mice PDF Download
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Author: Tze Peng Lim
Publisher:
ISBN:
Category : Dissertations, Academic
Languages : en
Pages : 286
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Author: Tze Peng Lim
Publisher:
ISBN:
Category : Dissertations, Academic
Languages : en
Pages : 286
Get Book Here
Book Description
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 23
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To understand the multi-step process of mammary tumorigenesis, we have compared gene expression profiles in different stages of mammary oncogenesis in MMTV-Wnt- 1 transgenic mice. Specifically, we have collected tissue samples from virgin mammary glands, hyperplastic mammary glands, Wnt- 1 mammary tumors, and tumors metastasized to the lung, and compared their gene expression patterns. Hierarchical clustering analysis and multidimensional scaling analysis showed that gene expression profiles are associated with tumor progression. Each sample group from the same stage cluster separately from samples at other stages. Using the statistical analysis permutation t-test, I identified groups of genes differentially expressed in each of the stages. I also identified a group of genes as potential direct or indirect target genes of Wnt signaling since they are only regulated in mammary tumors induced by the MMTV-Wnt-1 transgene in comparison with tumors induced by other transgenes such as (MMTV)-c-myc, MMTV-Ha-ras, MMTV-neu, MMTV-polyoma middle T antigen, C3(l)/simian virus 40 T/t antigen, and WAP-SV4O T/t antigen (Desai et al., 2002). In addition, I established gene expression profiles for mammary tumors induced by Wntl, and by Wnt1 in cooperation with loss of tumor suppressor genes such as Pten or P53.
Author: Stephen Hursting
Publisher:
ISBN:
Category :
Languages : en
Pages : 32
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Wnt-1 transgenic(TG) mice develop mammary tumors at a high rate by 1 year of age due to mammary gland overexpression of the Wnt-1 oncogene. - We have shown that p53-deficiency accelerates mammary tumorigenesis in these mice, with 100% of p53-1- Wnt-1 TG mice and p53+/-Wnt-1 TG mice dead from mammary tumors by 5 months and 9 months of age, respectively. To test their response to cancer preventive regimens, we randomized 104 female p53+/- Wnt-1 TG mice (5 weeks of age, 20 mice/treatment) to receive: 1) control diet (AIN-76A diet); 2) fenretinide (AIN 76A diet with 0.04% w/w fenretinide); 3) fluasterone (AIN- 76A diet with 0.2% fluasterone); 4) soy (AIN-76A diet with 0.45% phytochemical-enriched soy extract); or 5) a calorie restriction regimen (40% reduction in carbohydrate calorie intake relative to the control group). All mice were euthanized once a tumor reached 1.5 cm in diameter. We found that, relative to the control group (MTD=15.7 weeks), the fenretinide (MTD=23.1 weeks, p=O. Ol) and fluasterone (MTD=23.l weeks, p=O.006) and soy (MTD =21 weeks, p=O.04) groups displayed moderate but significant delays in tumor development and death, while the calorie restricted group (MTD> 40 weeks; p
Author: Bob Y. Liu
Publisher:
ISBN:
Category :
Languages : en
Pages : 164
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Author: Deepa Shankar
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ISBN:
Category :
Languages : en
Pages : 0
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Mouse mammary tumor virus (MMTV) is used as an insertion mutagen in transgenic mice that express the Wnt1 gene in their mammary gland, to produce additional events like activation of a second oncogene. Cloning cellular sequences flanking new proviral insertion from tumor 76 identified a common insertion locus for MMTV. Further analyses of this region identified Fgf3 as the gene activated over a long distance by MMTV. Fgf8 is another oncogene that I identified was activated in 10% of the mammary tumors form these infected Wnt1 transgenic mice. Fgf8 encodes for at least seven different protein isoforms, three of which were isolated by us. These three isoforms (Fgf8a, b & c) differ in their NIH3T3 cell transforming abilities. Fgf8b induces programmed cell death of mammary epithelial cells. This apoptotic property is not confined to Fgf8b but is also seen when mammary epithelial cells are treated with purified human FGF proteins (FGF 1, 2, 4, 6, & 9). Over expression of BCL2 in the mammary epithelial cells delays the onset of FGF induced apoptosis. Female transgenic mice expressing the Fgf8 gene in the mammary gland developed tumors with a latency of 5-6 months. These tumors were found to be adenocarcinomas: benign adenomas to invasive ductal carcinomas. Northern analyses of tumor RNAs show high expression of the transgene.
Author: Deepa Bhavani Shankar
Publisher:
ISBN:
Category :
Languages : en
Pages : 334
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Mouse mammary tumor virus (MMTV) is used as an insertion mutagen in transgenic mice that express the Wnt1 gene in their mammary gland, to produce additional events like activation of a second oncogene. Cloning cellular sequences flanking new proviral insertion from tumor 76 identified a common insertion locus for MMTV. Further analyses of this region identified Fgf3 as the gene activated over a long distance by MMTV. Fgf8 is another oncogene that I identified was activated in 10% of the mammary tumors form these infected Wnt1 transgenic mice. Fgf8 encodes for at least seven different protein isoforms, three of which were isolated by us. These three isoforms (Fgf8a, b & c) differ in their NIH3T3 cell transforming abilities. Fgf8b induces programmed cell death of mammary epithelial cells. This apoptotic property is not confined to Fgf8b but is also seen when mammary epithelial cells are treated with purified human FGF proteins (FGF 1, 2, 4, 6, & 9). Over expression of BCL2 in the mammary epithelial cells delays the onset of FGF induced apoptosis. Female transgenic mice expressing the Fgf8 gene in the mammary gland developed tumors with a latency of 5-6 months. These tumors were found to be adenocarcinomas: benign adenomas to invasive ductal carcinomas. Northern analyses of tumor RNAs show high expression of the transgene.
Author:
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Category :
Languages : en
Pages : 16
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WNT genes encode a large family of secreted signaling molecules essential for development and oncogenesis. wnt-1, the founding member of the wnt gene family, was initially identified as an oncogene which, upon ectopic expression induced by viral insertion, causes mammary tumorigenesis in mice, providing a potential model for studying human breast cancer. However, the Wnt- 1 receptor, an essential component mediating Wnt- 1 function, has not been identified, and the molecular and biochemical nature of the Wnt signaling pathway is not fully understood. In this proposal for the Career Development Award, we propose experiments combining molecular techniques and the axis duplication assay in the Xenopus embryo to answer the following two critical questions: 1) What is the receptor mediating Wnt- 1 oncogenic function? 2) How does the Dishevelled protein, which is an essential Wnt signaling component, transduce Wnt-1 signal? These experiments should provide a better understanding of the molecular nature of Wnt-1 signaling in mammary malignancy.
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Category :
Languages : en
Pages : 0
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Over expression of Wnt proteins has long been know to lead to mammary hyperplasia and neoplasia in the mouse mammary gland. Unregulated Wnt signaling may also contribute to the formation of human breast tumours as over expression of Wnt proteins and nuclear localization of 13-catenin has been reported. The experiments in this proposal are designed to identify the receptor proteins responsible for transduction of oncogenic Wnt signals in mammary cells. Possible candidates are members of the Frizzled, Notch and LRP families of transmembrane proteins as all have been suggested to act as Wnt receptors. A survey of the Frizzled, Notch and LRP proteins expressed in the mature virgin mammary gland of the mouse has been conducted to identify candidate receptors. Currently the ability of these proteins to interact physically with Wnt ligands is being tested in cross- linking and co-immunoprecipitation experiments. Also the ability of these proteins to transduce, and of dominant negative form to attenuate, a Wnt signal is being evaluated in a functional assay for Wnt signaling. Finally, a mammary specific transgene encoding a dominant negative Wnt receptor has been produced. This will be introduced into mice by pronuclear injection and tested for its ability to antagonize extracellular Wnt signals in mice and to prevent the onset of mammary hyperplasia and tumorigenesis caused by the Wnt-1 oncogene.
Author: Julie Anne Rudnicki
Publisher:
ISBN:
Category :
Languages : en
Pages : 202
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Author:
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ISBN:
Category : Genetics
Languages : en
Pages : 516
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