Molecular Mechanisms of SKP2 Targeting on Prostate Cancer Progression

SKP2靶向前列腺癌进展的分子机制

基本信息

批准号：
8261509
负责人：
Zhenbang Chen
金额：
$ 13.11万
依托单位：
MEHARRY MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-26 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8261509
关键词：
1-Phosphatidylinositol 3-Kinase Acute Adenocarcinoma Advanced Malignant Neoplasm Affect African American Age-Months American Androgens Apoptotic Binding Cancer Control Cancer Patient Castration Caucasians Caucasoid Race Cell Aging Cell Proliferation Cell Survival Cells Cessation of life Chromosomes Complex Data Death Rate Development Disease Down-Regulation E-Cadherin Embryo Epithelial Cells Ethnic group Fibroblasts Growth Homologous Gene Human In Vitro Incidence Investigation Knockout Mice Life Malignant Neoplasms Malignant neoplasm of prostate Mediating Molecular Mus Mutant Strains Mice Mutate Oncogenic Operative Surgical Procedures PC3 cell line PTEN gene Pathway interactions Phosphoric Monoester Hydrolases Phosphorylation Phosphotransferases Prostate Prostatic Intraepithelial Neoplasias Prostatic Neoplasms Proteins Proto-Oncogene Proteins c-akt Race Radiation therapy Recurrence Regulation Resistance Role SKP2 gene Serine Signal Pathway Skp2 Proteins Smooth Muscle Actin Staining Method Specificity TEP1 gene Testing The Vanderbilt-Ingram Cancer Center at the Vanderbilt University Ubiquitination Up-Regulation Wild Type Mouse Xenograft procedure cancer cell cancer diagnosis cancer health disparity cancer statistics deprivation in vivo inhibitor/antagonist male men mortality mouse model oncoprotein p21 overexpression response tumor tumor progression tumor xenograft tumorigenesis wortmannin

项目摘要

Prostate cancer (PCa) is a prevailing disease found in African American men, and is the most frequently diagnosed cancer in American men. African American males died of PCa in a 2.39-folder higher rate as compared with Caucasian males, while the average death rate due to all cancers was only 1.34-fold higher between these two races (Cancer Statistics 2010)(10). Surgery, radiation therapy and androgen-deprivation therapy have been developed and applied widely to control PCa; however, prostate cancer patients sfill died of Castration Resistant Prostate Cancer (CRPC). Molecular signaling pathways contributing to the initiation and progression of PCa; particulariy, the mechanism of CRPC grovirth remain to be elucidated in order to develop efficient strategies for cancer control. Aberrant regulation of Pten-P13K-Akt pathway, p53 loss and Skp2 activation are commonly found in CRPC. Further investigation on their roles in PCa progression will help us to understand the incidence and mortality rate of PCa, and the disparifies among ethnic and racial groups.

前列腺癌（PCa）是非洲裔美国男性中常见的疾病，也是美国男性中最常诊断出的癌症。与白人男性相比，非裔美国男性死于 PCa 的比率高出 2.39 倍，而这两个种族之间所有癌症的平均死亡率仅高出 1.34 倍（癌症统计数据 2010）(10)。手术、放射治疗和雄激素剥夺疗法已被开发并广泛应用于控制前列腺癌；然而，前列腺癌患者却死于去势抵抗性前列腺癌（CRPC）。促进 PCa 发生和进展的分子信号通路；特别是，CRPC grovirth 的机制仍有待阐明，以便开发有效的癌症控制策略。 CRPC 中常见 Pten-P13K-Akt 通路的异常调节、p53 丢失和 Skp2 激活。进一步研究它们在 PCa 进展中的作用将有助于我们了解 PCa 的发病率和死亡率以及民族和种族群体之间的差异。