Project 170984

Most deaths from prostate cancer (PCa) are due to metastases (cancer spread) in a form that is highly resistant to conventional therapies. There is an urgent need for more effective therapy to improve disease survival and management. Thus, we have been focusing on discovering new metastasis-associated genes that can be used as either as biomarker or therapeutic targets. In doing so, we have previously established SAGE (Serial Analysis of Gene Expression) libraries based on our unique prostate cancer models (i.e. a metastatic prostate cancer tissue subline (PCa1-met) and its non-metastatic counterpart (PCa2), both derived from one patient's cancer specimen). An analysis of this system has revealed that the regulator of G-protein signalling 1 (RGS1) gene is overexpressed in the metastatic subline. This finding was confirmed by both RT-PCR and immunohistochemical analysis of PCa1-met and PCa2 tumor tissues. Importantly, our preliminary data indicate that RGS1 protein is overexpressed in clinical samples of prostate cancer (PCa) relative to benign prostate. While RGS1 has not previously been associated with PCa, its mRNA and/or protein are reported to be highly expressed in several different types of carcinoma, including melanoma, cervical cancer, and head and neck squamous cell carcinoma; in particular, RGS1 overexpression is significantly correlated with sentinel lymph node metastasis. This suggests that the RGS1 gene plays a key role in the metastatic process. This study is aimed at proving the clinical relevance, functional importance and potential mechanism of RGS1 in prostate cancer and prostate cancer metastasis. Significance: This study may demonstrate that the RGS1 gene provides a new therapeutic target and/or prognostic tool for metastatic prostate cancer. If so, it could lead to urgently needed improvements in the management of the disease.

using SAGE libraries and human cancer xenografts to identify and validate RGS1 as a metastasis-associated gene in prostate cancer