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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：
8534732
负责人：
Zhenbang Chen
金额：
$ 11.74万
依托单位：
MEHARRY MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8534732
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 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 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 diagnosis cancer health disparity cancer statistics castration resistant prostate cancer deprivation in vivo inhibitor/antagonist male men mortality mouse model oncoprotein p21 overexpression prostate cancer cell 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)是一种在非裔美国人男性中发现的流行疾病，也是美国男性中最常被诊断出的癌症。非洲裔美国男性死于前列腺癌的比率比高加索男性高2.39倍，而这两个种族之间死于所有癌症的平均死亡率只高出1.34倍(癌症统计2010)(10)。手术、放射治疗和去雄激素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抗去势前列腺癌(CRPC)。参与PCa发生和发展的分子信号通路；尤其是CRPC的发生机制仍有待阐明，以期开发有效的癌症控制策略。CRPC中普遍存在Pten-P13K-Akt通路的异常调节、P53的丢失和Skp2的激活。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，以及不同民族和种族之间的差异。