METALLOTHIONEIN AND PROSTATE TUMORIGENESIS

金属硫蛋白和前列腺肿瘤发生

• 批准号: 6178001
• 负责人: Asim B Abdel-Mageed
• 金额: $ 7.4万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6178001
• 关键词: androgen receptor; athymic mouse; benign prostate hyperplasia; biomarker; carcinogenesis; clinical research; collagenase; diagnosis design /evaluation; fibroblast growth factor; gene expression; hormone therapy; human therapy evaluation; human tissue; immunocytochemistry; metallothionein; metastasis; neoplasm /cancer diagnosis; northern blottings; pathologic process; polymerase chain reaction; prostate neoplasms; prostate specific antigen; tissue /cell culture; western blottings

DESCRIPTION (adapted from the application) Despite significant research in the field of prostate cancer (PC), the disease remains elusive in terms of its etiology, pathology, pathogenesis and clinical management. Identification of new genotype and phenotypic markers and characterization of molecular mechanisms underlying promotion of latent PC to malignant and metastatic phenotypes would, therefore, be of paramount significance. Current evidence demonstrated the unequivocal relationship between the ubiquitous occurrence of metallothionein (MT) in various types of human primary tumors, such as prostate cancer, breast carcinoma and malignant melanoma, and metastasis and poor prognostic outcome. Our preliminary RT-PCR and immunohistochemical analyses have demonstrated enhanced MT gene expression in human PC biopsies when compared to tissue specimens from benign prostatic hyperplasia (BPH), suggesting that aberrant expression of this metalloprotein may potentially lead to immortalization and metastasis of prostate cells. We therefore hypothesized that MT plays a pivotal role in promotion of neoplastic cell growth and in progression of the latent disease to metastatic PC. In this proposal, (1) the correlation between MT expression in biopsy specimens from P patients and disease progression will be established using both qualitative an quantitative measures; (2) the potential use of serum and/or seminal plasma MT levels as a biomarker for disease progression will be evaluated in an attempt to develop a more discriminatory marker than prostate specific antigen (PSA) for distinguishing latent from aggressive cancer; and (3) the role of MT in modulating mechanisms underlying neoplastic growth, metastasis and refractoriness to hormonal therapy will be delineated using both in vitro and in vivo approaches. We believe that the data generated from this proposed stud will not only strengthen our basic understanding about the disease progression but will also provide a new frontier for development of a novel diagnostic and a potential therapeutic approach for treatment of PC.

描述（改编自应用程序）