Project 2: Molecular Regulation of Kaiso in Prostate Cancer

7.项目总结/摘要 虽然前列腺腺癌是美国男性中最常见的癌症， 比预期的要低患有前列腺癌（PCa）的非洲裔美国人（AAs） 通常有更积极的疾病，并弥补了不成比例的死亡人数， 疾病;然而，许多患有PCa的患者即使未经治疗也不会死于PCa（即，惰性前列腺 癌症）。我们最近研究了分子Kaiso在PCa中的表达，发现Kaiso在PCa中的表达与PCa的表达相关。 积极的PCa增加，尤其是在AAs的PCa。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），并通过这种特定基因的沉默， 导致上皮细胞向间质细胞转化（EMT）和前列腺癌的雄激素抗性。我们的目标 该提案旨在证明Kaiso的核表达是通过EGFR信号传导介导的， Kaiso可以在治疗上靶向减少EMT和相关的PCa转移。完成 为此，我们概述了三个具体目标。

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.