Project 2: Molecular Regulation of Kaiso in Prostate Cancer

项目2：Kaiso对前列腺癌的分子调控

基本信息

批准号：
9211123
负责人：
Clayton Yates
金额：
$ 12.94万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-09-30 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9211123
关键词：
African American Alabama Androgens Apoptosis Binding Cancer Death Rates Cancer Patient Castration Cell Cycle Arrest Cell Nucleus Cell Proliferation Cells Cessation of life DNA Methylation Development Diagnostic Disease E-Cadherin Epidermal Growth Factor Receptor Epigenetic Process Evaluation Gene Deletion Genes Genetic Indolent Institution Investigation Link Malignant Epithelial Cell Malignant neoplasm of prostate Mediating Methylation Molecular Morehouse School of Medicine Mus Neoplasm Metastasis Nuclear Patients Peptides Phenotype Primary Neoplasm Prostate Adenocarcinoma Proteins Receptor Signaling Regulation Repressor Proteins Resistance Role Secondary to Signal Transduction Testing Therapeutic Universities Xenograft Model autocrine base cancer diagnosis chromatin immunoprecipitation design epithelial to mesenchymal transition inhibitor/antagonist male novel pre-clinical prevent prognostic prostate cancer cell line protein protein interaction tumor tumor growth

项目摘要

7. PROJECT SUMMARY/ABSTRACT Although prostatic adenocarcinoma is the most commonly diagnosed cancer in U.S. males, the death rate from this cancer is lower than would be expected. African Americans (AAs) who have prostate cancer (PCa) typically have more aggressive disease and make up a disproportionate number of the deaths from this disease; however, many patients with PCa will not die of PCa even if untreated (i.e., indolent prostate cancer). We have recently studied the expression of the molecule, Kaiso, in PCa and found that Kaiso is increased in aggressive PCa, especially in PCa in AAs. Also, we have found that Kaiso is involved in facilitating the epigenetic suppression of genes (e.g., E-cadherin), and via this silencing of specific genes, causing epithelial to mesenchymal transition (EMT) and androgen resistance of PCa. The objectives of our proposal are to demonstrate that the nuclear expression of Kaiso is mediated through EGFR signaling and that Kaiso can be targeted therapeutically to reduce EMT and associated metastases of PCa. To accomplish this, we have outlined three specific aims.

7。项目摘要/摘要尽管前列腺腺癌是美国男性最常见的癌症，但死亡率从这个癌症中比预期的要低。患有前列腺癌（PCA）的非裔美国人（AAS）通常患有更多的侵略性疾病，构成了这一死亡的数量不成比例疾病;但是，即使未经治疗，许多患有PCA的患者也不会死于PCA（即，顽固的前列腺癌症）。我们最近在PCA中研究了分子Kaiso的表达，发现Kaiso是侵略性PCA增加，尤其是在AAS中的PCA中。另外，我们发现Kaiso参与了促进基因的表观遗传抑制（例如E-钙粘蛋白），并通过对特定基因的沉默，导致上皮上皮过渡（EMT）和PCA的雄激素耐药性。我们的目标提案是要证明Kaiso的核表达是通过EGFR信号传导和可以将Kaiso靶向治疗，以减少PCA的EMT和相关转移。完成这，我们概述了三个具体目标。