METALLOTHIONEIN AND PROSTATE TUMORIGENESIS

金属硫蛋白和前列腺肿瘤发生

• 批准号: 2743712
• 负责人: Asim B Abdel-Mageed
• 金额: $ 7.35万
• 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 2001-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2743712
• 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） 尽管在前列腺癌 (PC) 领域进行了大量研究， 该疾病的病因、病理、发病机制仍然难以捉摸 和临床管理。 新基因型和表型的鉴定 促进的分子机制的标记和表征 因此，潜伏性 PC 与恶性和转移表型的关系是： 至高无上的意义。 目前的证据明确表明 金属硫蛋白（MT）在体内普遍存在之间的关系 各种类型的人类原发性肿瘤，如前列腺癌、乳腺癌 癌和恶性黑色素瘤，以及转移和不良预后 结果。 我们的初步 RT-PCR 和免疫组织化学分析表明 与相比，人类 PC 活检中 MT 基因表达增强 良性前列腺增生 (BPH) 的组织标本表明 这种金属蛋白的异常表达可能会导致 前列腺细胞的永生化和转移。 因此我们假设 MT 在促进肿瘤细胞生长和 潜伏性疾病进展为转移性 PC。 在本提案中，(1) P患者活检标本中MT表达的相关性 疾病进展将通过定性和 定量措施； (2) 血清和/或精浆的潜在用途 MT 水平作为疾病进展的生物标志物将在 尝试开发比前列腺特异性更具区分性的标记物 抗原（PSA）用于区分潜伏性癌症和侵袭性癌症；和（3） MT 在调节肿瘤生长、转移机制中的作用 并且对激素治疗的无效性将使用两者来描述 体外和体内方法。 我们相信由此产生的数据 拟议的螺柱不仅会加强我们对 疾病进展，但也将为发展提供新的前沿 一种治疗 PC 的新诊断和潜在治疗方法。