The Role of Phosphatase of Regenerating Liver-3 in Alcohol-Associated Disease

再生肝磷酸酶 3 在酒精相关疾病中的作用

• 批准号: 8308180
• 负责人: Mark W. Zimmerman
• 金额: $ 4.22万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8308180
• 关键词: Abbreviations; Adenomatous Polyposis Coli; Affect; Alcohol-Induced Disorders; Alcohols; Animal Model; Animals; Azoxymethane; Biological; Bromodeoxyuridine; Cell Proliferation; Colorectal Cancer; Disease; Drug Delivery Systems; Embryo; Endothelial Cells; Enzymes; Ethanol; Ethanol toxicity; Family; Frequencies; Gastrointestinal tract structure; Gene Targeting; Genes; Goals; Intestines; Knock-out; Knockout Mice; Lead; Life; Malignant - descriptor; Malignant Neoplasms; Mediating; Mediator of activation protein; Organ; Phenotype; Play; Process; Protein Tyrosine Phosphatase; Regulation; Reporting; Research; Research Proposals; Role; Sodium Dextran Sulfate; Tissues; alcohol abuse therapy; alcohol exposure; alcohol measurement; alcohol response; angiogenesis; cell motility; in vivo; innovation; intestinal epithelium; intraperitoneal; mouse model; novel; novel strategies; phosphatase of regenerating liver; stem; therapeutic target; tumor; tumor progression; tumorigenesis

DESCRIPTION (provided by applicant): The goal of this research proposal is to determine the role of Phosphatase of Regenerating Liver-3 (also known as PRL-3) in the biological response to alcohol exposure and toxicity. The PRL family of enzymes has become widely studied due to their potential roles in cancer and malignant disease, yet little is known and their function and regulation in vivo. Strong evidence indicates that PRL-3 is a mediator of several phenotypes elicited by ethanol exposure such as enhanced intestinal cell proliferation, angiogenesis, and cancers of the upper and lower digestive tract. These observations combined with our preliminary studies have indicated that there is a potential role for PRL-3 in mediating the phenotypes of alcohol exposure as well as alcohol-induced colorectal cancer. To study the role of PRL-3 in ethanol action, I have created a novel gene-targeted animal model can produce global and tissue-specific PRL-3 knockout mice. Using the knockout mouse model, the contribution of PRL-3 to alcohol-induced intestinal damage and alcohol-induced colorectal cancer will be assessed. These studies will ultimately lead to a better understanding of a gene potentially involved in the biological response to alcohol exposure as well as a potentially validating PRL-3 as a therapeutic target for the treatment of alcohol-induced colorectal cancer.

描述（由申请人提供）：本研究提案的目的是确定再生肝磷酸酶-3（PRL-3）在酒精暴露和毒性生物学反应中的作用。由于其在癌症和恶性疾病中的潜在作用，PRL酶家族已被广泛研究，但对其在体内的功能和调节知之甚少。强有力的证据表明，PRL-3是由乙醇暴露引起的几种表型的介质，例如增强的肠细胞增殖、血管生成和上消化道和下消化道的癌症。这些观察结果与我们的初步研究相结合，表明PRL-3在介导酒精暴露的表型以及酒精诱导的结直肠癌中具有潜在作用。为了研究PRL-3在乙醇作用中的作用，我建立了一种新的基因靶向动物模型，可以产生全局和组织特异性的PRL-3敲除小鼠。使用基因敲除小鼠模型，将评估PRL-3对酒精诱导的肠损伤和酒精诱导的结肠直肠癌的贡献。这些研究将最终导致更好地了解可能参与对酒精暴露的生物学反应的基因，以及可能验证PRL-3作为治疗酒精诱导的结直肠癌的治疗靶点。