Metastasis-related genes in prostate cancer: the role of caveolin-1

Prostate cancer continues to be a significant cause of death in U.S. men despite screening of asymptomatic men and extensive treatment with potentially curative therapies, predominantly radical prostatectomy and irradiation therapy. The reason for the persistent mortality resides in part in the presence of occult metastases at the time of treatment. Currently there are no curative therapies for metastatic prostate cancer. To better understand the metastatic phenotype in prostate cancer, we developed a strategy to compare and isolate mRNAs that are expressed differentially in cell lines derived from primary versus metastatic mouse prostate cancer using differential display-PCR. This strategy has proven to be successful and multiple gene sequences associated with metastasis in this model are being investigated. One of the genes isolated by this method was caveolin-1. Caveolin-1 was found to be overexpressed not only in metastatic mouse prostate cancer, but also human metastatic disease. Recent studies have indicated that suppression of caveolin expression induces androgen sensitivity in high-caveolin, androgen-insensitive mouse prostate cancer cells derived from metastases. Overexpression of caveolin leads to androgen insensitivity in low-caveolin, androgen-sensitive mouse prostate cancer cells. Caveolin-1, therefore, is a metastasis-related gene and a candidate gene for hormone-resistant prostate cancer in man.