METALLOTHIONEIN AND PROSTATE TUMORIGENESIS

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， 疾病的病因、病理、发病机制 临床管理。 新基因型和表型的鉴定 标记和表征的分子机制，促进 因此，潜在PC恶性和转移表型将是 最重要的意义。 目前的证据表明， 金属硫蛋白（MT）的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、乳腺 癌和恶性黑色素瘤，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 在人类PC活检组织中， 良性前列腺增生（BPH）的组织标本，这表明， 这种金属蛋白的异常表达可能导致 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促进肿瘤细胞增殖中起着关键作用， 潜伏性疾病进展为转移性PC。 在本建议中，（1） P患者活检标本中MT表达的相关性 和疾病进展将使用定性和 定量测量;（2）血清和/或精浆的潜在用途 作为疾病进展的生物标志物的MT水平将在一项研究中进行评估。 试图开发一种比前列腺特异性标记物更具区分性的标记物 用于区分潜伏性与侵袭性癌症的抗原（PSA）;和（3） MT在调节肿瘤生长、转移机制中的作用 和对激素治疗的难治性将使用 体外和体内方法。 我们认为，由此产生的数据 建议的研究不仅会加强我们对 疾病进展，但也将提供一个新的前沿发展， 一种新的诊断和潜在的治疗PC的方法。

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.