Beta-Catenin and Prostate Development

β-连环蛋白和前列腺发育

基本信息

批准号：
8063636
负责人：
CHAD M. VEZINA
金额：
$ 15.49万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8063636
关键词：
Adherens Junction Adhesions Advisory Committees Agonist Androgen Receptor Androgens Award Back Benign Prostatic Hypertrophy Biological Factors Biological Models Cadherins Cancer Biology Cell Adhesion Chemicals Comprehensive Cancer Center Data Development Development Plans Ductal Embryo Environment Epithelium FGF10 gene Future Genetic Transcription Goals Gonadal Steroid Hormones Grant Growth Growth and Development function In Vitro LacZ Genes Link Malignant neoplasm of prostate Mediating Mentors Mesenchyme Modeling Mus Mutant Strains Mice National Institute of Diabetes and Digestive and Kidney Diseases Organ Organ Culture Techniques Plasmids Probability Prostate Prostatic Prostatic Diseases Proteins Regulation Reporter Research Research Personnel Scientist Signal Pathway Signal Transduction Stretching Testing Training Universities Urogenital Sinus Urology Wisconsin Writing beta catenin career development cell motility clinically relevant fibroblast growth factor 10 in vivo inhibitor/antagonist male meetings mutant protein expression research and development

项目摘要

DESCRIPTION (provided by applicant): My goal as an independent researcher is to use a two-pronged approach to study prostate disease: (1) I will use the developing prostate as a model system for elucidating previously unrecognized signaling pathways that contribute to prostate growth and (2) I will investigate these signaling pathways in clinically relevant models of benign prostate hyperplasia or prostate cancer. My research focus in this proposal is to test the overarching hypothesis that beta-catenin is required for prostate ductal development in the embryonic mouse prostate anlagen, the urogenital sinus (UGS). The first two specific aims will investigate the function of beta-catenin during prostatic budding. They will test hypotheses that (1) androgens stimulate beta-catenin-mediated transcription in the UGS and that beta-catenin is required for budding, and (2) beta-catenin mediates cell adhesion during prostatic bud formation and that this action of beta-catenin is required for budding. The last aim investigates the regulation of beta-catenin during budding. It will test the hypothesis that (3) fibroblast growth factor 10 is required for stabilizing beta-catenin during prostatic budding. This research plan has a high probability of leading to the identification of beta-catenin as a central player in prostatic budding. My plan is to use the above results as preliminary data to apply, in year 3 of this award, for an RO1 or R03 grant focused on mechanisms of benign prostate hyperplasia or prostate cancer. As a K01 recipient, I will follow a career development plan with very specific research and development milestones for each award year. I will meet regularly with my mentors and advisory committee and complete didactic coursework in cancer biology. I will obtain experiential training in grant writing, Wnt/ beta-catenin signaling, benign prostate hyperplasia, and prostate cancer. This plan will stretch my research expertise and enhance my training in prostate disease research. The University of Wisconsin is an NIDDK-sponsored O'Brien Urology Research Center, an NCI-sponsored Comprehensive Cancer Center, and boasts nearly 40 prostate research labs, culminating in an ideal training environment for me as a future prostate scientist. Biological factors regulating growth during prostate development are also believed to be responsible for inappropriate growth during prostate disease. The proposed research will investigate how the beta-catenin protein interacts with male sex hormones to control prostate development, as these interactions might provide clues for how inappropriate prostate growth is activated during prostate disease.

描述（由申请人提供）：作为独立研究人员，我的目标是使用两种基准的方法来研究前列腺疾病：（1）我将使用发育的前列腺作为模型系统来阐明先前未识别的信号传导途径，从而有助于前列腺生长，并且（2）我将研究这些信号传导途径在良性前列腺过度倍增过度或前列腺癌的临床相关模型中。我在该提案中的研究重点是检验总体假设，即β-catenin对于胚胎小鼠前列腺前列腺前列腺的导管发育所必需的β-catenin，即泌尿生殖器窦（UGS）。前两个具体目的将研究前列腺发芽期间β-catenin的功能。他们将检验（1）雄激素刺激UGS中β-catenin介导的转录的假设，并且 β-catenin是萌芽所必需的，（2）β-catenin在前列腺芽形成过程中介导细胞粘附，并且β-catenin的这种作用是萌芽所必需的。最后一个目标调查了在萌芽过程中对β-catenin的调节。它将检验以下假设：（3）在前列腺发芽期间稳定β-catenin所必需的成纤维细胞生长因子10。该研究计划很有可能导致将β-catenin鉴定为前列腺萌芽中的核心参与者。我的计划是将上述结果用作初步数据，以在本奖项的第3年中应用RO1或R03赠款，该赠款重点介绍了良性前列腺增生或前列腺癌的机制。作为K01接收者，我将遵循一个职业发展计划，每个奖励年度都有非常具体的研发里程碑。我将定期与导师和咨询委员会会面，并完成癌症生物学的教学课程。我将获得赠款写作，WNT/β-catenin信号传导，良性前列腺增生和前列腺癌的体验培训。该计划将扩大我的研究专业知识，并增强我在前列腺疾病研究方面的培训。威斯康星大学是NIDDK赞助的O'Brien泌尿外科研究中心，NCI赞助的综合癌症中心，拥有近40个前列腺研究实验室，最终在理想的培训环境中成为我作为未来前列腺科学家的理想培训环境。还认为调节前列腺发育过程中增长的生物因素是造成前列腺疾病期间不适当生长的原因。拟议的研究将研究如何 β-catenin蛋白与男性性激素相互作用以控制前列腺发育，因为这些相互作用可能会为前列腺疾病期间如何激活前列腺生长如何激活。