Molecular Pathways in Hormone-Refractory Prostate Cancer
Annual rept. 1 Oct 1998-30 Sep 1999
BAYLOR COLL OF MEDICINE HOUSTON TX
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The natural history of prostate cancer involves progression to metastasis and the eventual development of hormone refractory disease. Multiple genetic activities are involved in the molecular cascade that leads to hormone resistance in prostate cancer. One of the gene products we found to be associated with metastasis in a mouse model as well as in human prostate cancer is caveolin-1. Orthotopic tumors with stable mouse prostate cancer clones with antisense caveolin-1 have reduced metastatic activities relative to vector-control clones and parent cell lines. Antisense caveolin clones significantly regressed in response to surgical castration in vivo. The antisense caveolin tumors that responded to castration therapy demonstrated increased levels of caveolin-1 and apoptosis relative to either vector-control clones or parental cell lines. Our data indicate that reduction of caveolin-1 levels not only suppresses metastatic activity but also restores androgen sensitivity. We have developed in vitro models to further define the pathways to hormone resistance that utilize caveolin-1. Our novel results establish a new paradigm for understanding androgen refractory disease and open the door for new innovations in prostate cancer therapy.
- Medicine and Medical Research