METALLOTHIONEIN AND PROSTATE TUMORIGENESIS

说明(改编自应用程序) 尽管在前列腺癌(PC)领域进行了大量研究，但 这种疾病在病因、病理学、发病机制等方面仍然难以捉摸 和临床管理。新基因型和新表型的鉴定 促进基因表达的分子机制的标记和表征 因此，恶性和转移性的潜伏性PC表型 最重要的意义。目前的证据表明， 金属硫蛋白(MT)在中国的普遍存在与其关系 人类各种类型的原发肿瘤，如前列腺癌、乳腺癌 癌和恶性黑色素瘤与转移和预后不良 结果。我们初步的RT-PCR和免疫组织化学分析表明 比较人PC活检组织中MT基因的表达增强 良性前列腺增生症(BPH)的组织标本，提示 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方面起着关键作用，在 潜伏期疾病进展为转移性PC。在本建议中，(1) P患者活检标本中MT表达的相关性研究 并将使用定性和定量两种方法确定疾病进展 定量测量；(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 试图开发一种比前列腺特异性更具区别性的标志物 用于区分潜伏性和侵袭性癌症的抗原(PSA)；和(3) MT在调节肿瘤生长、转移机制中的作用 对激素治疗的耐受性将用两种方法描述 体外和体内的方法。我们认为由此产生的数据 建议的研究不仅将加强我们对 疾病的发展，但也将提供一个新的前沿发展 一种治疗PC的新的诊断和治疗方法。

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.