权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Prx1 in malignant progression of prostate cancer

Prx1在前列腺癌恶性进展中的作用

基本信息

批准号：
7579045
负责人：
CANDACE S JOHNSON
金额：
$ 31.11万
依托单位：
ROSWELL PARK CANCER INSTITUTE CORP
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-04-05 至 2011-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7579045
关键词：
Address Affect Androgen Receptor Androgens Antioxidants Apoptosis Base Sequence Binding Biological Biological Assay Blood Vessels Cancer Etiology Cell Culture System Cell Hypoxia Cell Line Cell Proliferation Cell Survival Cells Cessation of life Chromatin Chronic Clinical Cloning Data Deletion Mutagenesis Deoxyribonuclease I Development Dimerization EMSA Elements Employee Strikes Environment Family Gene Targeting Generations Genes Gleason Grade for Prostate Cancer Human Hypoxia In Vitro Knowledge Laboratories Ligand Binding Malignant - descriptor Malignant Neoplasms Malignant neoplasm of prostate Mediating Messenger RNA Metastatic Prostate Cancer Microelectrodes Molecular Molecular Profiling Monitor Neoplasm Metastasis Nuclear Nucleic Acid Regulatory Sequences Outcome Oxidation-Reduction Oxidative Stress PC3 cell line Pattern Phenotype Printing Prostate Prostate Cancer therapy Prostate-Specific Antigen Protein Family Proteins Proteome Proteomics Reactive Oxygen Species Receptor Activation Regulation Research Research Personnel Resistance Role Second Primary Cancers Signaling Molecule Stress Sulfhydryl Compounds Testing Therapeutic Time Tissues Transcriptional Regulation base cancer cell cancer therapy chromatin immunoprecipitation clinically significant deprivation design foot human tissue in vitro activity in vivo mRNA Expression member men novel novel therapeutic intervention oxidation oxidative damage peroxiredoxin pressure prognostic indicator programs promoter receptor binding research study response sound transcription factor tumor tumor growth tumor progression

项目摘要

Prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer death in men in the US. Recent studies demonstrated that prostate cancer cells grow in a chronic or transient hypoxic microenvironment. A correlation between the extent of tumor hypoxia and poor clinical outcome has also been demonstrated. More recently, androgen deprivation, the most common form of prostate cancer therapy, was itself shown to generate a state of transient hypoxia in prostate cancer. Two highly homologous members of the peroxiredoxin protein family, Prx1 and Prx2, have been shown to affect cell proliferation/apoptosis and increase the stress resistance in cancer cells. However, the effects of Prx expression in human cancers, their influence on cancer therapy, and the regulatory basis of their expression in cancer have not been investigated. Because these Prxs can be predicted to have a significant impact on prostate cancer, the PI has recently undertaken studies of Prx1/2 in prostate cancer. The research proposed in this application emanates from our recent studies of Prx1/2 regulation and function in human prostate cancer cells and tissues. The observations made in the Pi's laboratory led us to postulate that Prx1 possesses unique functions and regulatory mechanisms in human prostate cancer that significantly influences its malignant progression. Our preliminary data described herein provide compelling support of this prediction. It is hypothesized that hypoxia-induced oxidative stress in tumors up-regulates Prx1 expression via activating the redox-sensitive transcriptional factors and signaling molecules and that the dysregulated activation of these regulatory components leads to a constitutive Prx1 elevation in a subset of cancer cells. It is also hypothesized thatihe elevated Prx1 in these cells provides them with aggressive survival phenotypes, in part by directly reducing ROS and oxidative damage, and also by increasing prostate specific antigen (PSA) expression and androgen receptor (AR) activity. It is further hypothesized that the functions of Prx1 are mediated by its ability to control the oxidation/function of redox-sensitive molecules that in turn contribute to the malignant progression of prostate cancer. Three Specific Aims are proposed to test these hypotheses. In Aim 1, we will establish the molecular basis for Prx1 elevation in human prostate cancer cells. In Aim 2, we will determine the functional significance of Prx1 in malignant progression of prostate cancer cells. In particular, we will investigate the novel role for Prx1 in regulating PSA expression and AR activity in response to hypoxia. In Aim 3, we will identify important redox-sensitive target/effector molecules that mediate the Prx1 functions to promote malignant progression of prostate cancer. The objective of the proposed research is to define the role ofPrxl in hypoxia-response of prostate cancer and the underlying regulatory mechanisms involved. This study will also provide a soundscientific basis upon which the role ofPrxl canbe elucidatedin prostate cancer, enabling the development of novelprognostic/therapeutic approaches to inhibit its malignant progression.

前列腺癌是最常见的非皮肤癌症，也是美国癌症死亡的第二大原因