METALLOTHIONEIN AND PROSTATE TUMORIGENESIS

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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.