Project 2: Molecular Regulation of Kaiso in Prostate Cancer

7.项目摘要/摘要 虽然前列腺癌是美国男性最常见的癌症，但死亡率 这种癌症的发病率低于预期。患有前列腺癌的非裔美国人(AA) 通常有更具侵袭性的疾病，并在因此而死亡的人数中占不成比例 疾病；然而，许多前列腺癌患者即使不接受治疗(即惰性前列腺)也不会死于前列腺癌 癌症)。我们最近研究了Kaiso分子在前列腺癌中的表达，发现Kaiso是 侵袭性前列腺癌增加，尤其是腹主动脉硬化。此外，我们还发现凯索参与了 促进基因的表观遗传抑制(例如，E-钙粘附素)，并通过这种特定基因的沉默， 导致PCa上皮向间充质转化(EMT)和雄激素抵抗。我们的目标是 建议证明Kaiso的核表达是通过EGFR信号和 Kaiso可以作为治疗的靶点，以减少EMT和相关的PCa转移。要完成 为此，我们勾勒出了三个具体目标。

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.