11 research outputs found

    Epithelial Hic-5/ARA55 expression contributes to prostate tumorigenesis and castrate responsiveness

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    Stromal–epithelial interactions dictate prostate tumorigenesis and response to castration. Hydrogen peroxide-inducible clone 5 (Hic-5/ARA55) is a transforming growth factor-beta (TGF-β)-induced coactivator of androgen receptor (AR) expressed in the prostate stroma. Interestingly, following castration, we identified epithelial expression of Hic-5/ARA55 in mouse and human prostate tissues. To determine the role of epithelial Hic-5 in prostate cancer progression and castration responsiveness, we compared LNCaP cells having Hic-5 stably expressed with the parental LNCaP cells following tissue recombination xenografts with mouse prostate stromal cells. We previously identified knocking out prostate stromal TGF-β signaling potentiated castrate-resistant prostate tumors, in a Wnt-dependent manner. The LNCaP chimeric tumors containing prostate fibroblasts conditionally knocked out for the TGF-β type II receptor (Tgfbr2-KO) resulted in larger, more invasive, and castration-resistant tumors compared those with floxed (control) stromal cells. However, the LNCaP-Hic5 associated with Tgfbr2-KO fibroblasts generated chimeric tumors with reduced tumor volume, lack of invasion and restored castration dependence. Neutralization of canonical Wnt signaling is shown to reduce prostate tumor size and restore regression following castration. Thus, we hypothesized that epithelial Hic-5/ARA55 expression negatively regulated Wnt signaling. The mechanism of the Hic-5/ARA55 effects on castration was determined by analysis of the c-myc promoter. C-myc luciferase reporter activity suggested Hic-5/ARA55 expression inhibited c-myc activity by β-catenin. Sequential ChIP analysis indicated β-catenin and T-cell-specific 4 (TCF4) bound the endogenous c-myc promoter in the absence of Hic-5 expression. However, the formation of a TCF4/Hic-5 repressor complex inhibited c-myc promoter activity, by excluding β-catenin binding with TCF4 on the promoter. The data indicate Hic-5/ARA55 expression in response to castration-enabled epithelial regression through the repression of c-myc gene at the chromatin level

    Promoting Food Security in Rwanda through Sustainable Agricultural Productivity: Meeting the Challenges of Population Pressure, Land Degradation, and Poverty

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    The horror of genocide and civil war have turned the world's attention to Rwanda over the last year. But before and beyond that conflict, there was hunger and the slow grinding poverty of small holder agriculture meeting with severe land scarcity and degradation. This report is about reversing the spiraling decline of the land and the economy in rural Rwanda. Three things conspire to accelerate this decline: unsustainable land use practices, insufficient non-farm employment, and rapid population growth. We focus on the forces behind productivity decline in Rwandan agriculture. This report examines how erosion, organic input use, soil conservation investments, use of fertilizer and lime, and land use strategies affect productivity. We then examine what determines farmers; productivity and conservation investments. The results are based on collaborative research between the Rwandan Ministry of Agriculture (MINAGRI) and Michigan State University. The data derive from a detailed farm-level survey, one of the most comprehensive in Africa, conducted by the Division des Statistiques Agricoles (DSA/MINAGRI). The survey covered a nationwide random sample of 1248 households, and was undertaken of 11 years, from 1984-1994. DSA has been, and we hope will be again, one of the national treasures of Rwanda. Our key findings are that Rwandan framers need to sustainable intensify their farming by protecting the soil against erosion, and by enhancing soil fertility through the use of organic matter, and chemical fertilizer, and lime. Without more input access and use, inevitable intensification of farming, as holding grow smaller, will be based only on adding more labor and cropping more intensely, both of which will degrade soils and lead to greater hardship. Where farmers are now making these investments, we report successes. We find success is often predicted on confidence in the future, knowledge from extension services, cash and labor resources from off-farm earnings, holding livestock that provides manure, and planting perennial cash crops. The contributions of this report are: (1) in underscoring and focusing on priority strategies and questions regarding the many issues that have come in and out of development debate in the highland tropics of Africa, and (2) in the systematic application of detailed, nationwide survey data to these key questions. Moreover, the report points to the great value of excellent national agricultural statistics services and national capacity to analyze data and provide insights for policy debate

    Promoting Food Security in Rwanda Through Sustainable Agricultural Productivity: Meeting the Challenges of Population Pressure, Land Degradation, and Poverty

    No full text
    The horror of genocide and civil war have turned the world's attention to Rwanda over the last year. But before and beyond that conflict, there was hunger and the slow grinding poverty of small holder agriculture meeting with severe land scarcity and degradation. This report is about reversing the spiraling decline of the land and the economy in rural Rwanda. Three things conspire to accelerate this decline: unsustainable land use practices, insufficient non-farm employment, and rapid population growth. We focus on the forces behind productivity decline in Rwandan agriculture. This report examines how erosion, organic input use, soil conservation investments, use of fertilizer and lime, and land use strategies affect productivity. We then examine what determines farmers; productivity and conservation investments. The results are based on collaborative research between the Rwandan Ministry of Agriculture (MINAGRI) and Michigan State University. The data derive from a detailed farm-level survey, one of the most comprehensive in Africa, conducted by the Division des Statistiques Agricoles (DSA/MINAGRI). The survey covered a nationwide random sample of 1248 households, and was undertaken of 11 years, from 1984-1994. DSA has been, and we hope will be again, one of the national treasures of Rwanda. Our key findings are that Rwandan framers need to sustainable intensify their farming by protecting the soil against erosion, and by enhancing soil fertility through the use of organic matter, and chemical fertilizer, and lime. Without more input access and use, inevitable intensification of farming, as holding grow smaller, will be based only on adding more labor and cropping more intensely, both of which will degrade soils and lead to greater hardship. Where farmers are now making these investments, we report successes. We find success is often predicted on confidence in the future, knowledge from extension services, cash and labor resources from off-farm earnings, holding livestock that provides manure, and planting perennial cash crops. The contributions of this report are: (1) in underscoring and focusing on priority strategies and questions regarding the many issues that have come in and out of development debate in the highland tropics of Africa, and (2) in the systematic application of detailed, nationwide survey data to these key questions. Moreover, the report points to the great value of excellent national agricultural statistics services and national capacity to analyze data and provide insights for policy debate

    Promoting Food Security in Rwanda Through Sustainable Agricultural Productivity: Meeting the Challenges of Population Pressure, Land Degradation, and Poverty

    No full text
    The horror of genocide and civil war have turned the world's attention to Rwanda over the last year. But before and beyond that conflict, there was hunger and the slow grinding poverty of small holder agriculture meeting with severe land scarcity and degradation. This report is about reversing the spiraling decline of the land and the economy in rural Rwanda. Three things conspire to accelerate this decline: unsustainable land use practices, insufficient non-farm employment, and rapid population growth. We focus on the forces behind productivity decline in Rwandan agriculture. This report examines how erosion, organic input use, soil conservation investments, use of fertilizer and lime, and land use strategies affect productivity. We then examine what determines farmers; productivity and conservation investments. The results are based on collaborative research between the Rwandan Ministry of Agriculture (MINAGRI) and Michigan State University. The data derive from a detailed farm-level survey, one of the most comprehensive in Africa, conducted by the Division des Statistiques Agricoles (DSA/MINAGRI). The survey covered a nationwide random sample of 1248 households, and was undertaken of 11 years, from 1984-1994. DSA has been, and we hope will be again, one of the national treasures of Rwanda. Our key findings are that Rwandan framers need to sustainable intensify their farming by protecting the soil against erosion, and by enhancing soil fertility through the use of organic matter, and chemical fertilizer, and lime. Without more input access and use, inevitable intensification of farming, as holding grow smaller, will be based only on adding more labor and cropping more intensely, both of which will degrade soils and lead to greater hardship. Where farmers are now making these investments, we report successes. We find success is often predicted on confidence in the future, knowledge from extension services, cash and labor resources from off-farm earnings, holding livestock that provides manure, and planting perennial cash crops. The contributions of this report are: (1) in underscoring and focusing on priority strategies and questions regarding the many issues that have come in and out of development debate in the highland tropics of Africa, and (2) in the systematic application of detailed, nationwide survey data to these key questions. Moreover, the report points to the great value of excellent national agricultural statistics services and national capacity to analyze data and provide insights for policy debate.Food Security and Poverty, Land Economics/Use, Productivity Analysis, Downloads July 2008-July 2009: 54,
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