Molecular Pathways in Hormone-Refractory Prostate Cancer
Final rept. 1 Oct 1998-31 Mar 2001
BAYLOR COLL OF MEDICINE HOUSTON TX
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We have identified and characterized the expression of caveolin-1 cav-1 a gene related to prostate cancer metastasis and hormone independence. We proposed to elucidate the molecular pathway of castration-induced regression and the mechanism of caveolin-1 mediated hormone resistance. We attempted to develop novel therapeutic approaches for hormone refractory prostate cancer based on this new information. These studies were designed to confirm the role of caveolin-1 in androgen independent prostate cancer and identify novel therapeutic approaches to androgen insensitive prostate cancer. Expression of caveolin-1 under hormonal regulation. Overexpression of caveolin-1 confers androgen insensitivity and increased cell viability. Suppression of caveolin-1 can restore androgen sensitivity and decrease cell survivalclonogenicity. Caveolin-1 is secreted by mouse and human metastatic prostate cancer cells and may have paracrine andor autocrine anti-apoptotic activities. Further studies indicate that antibody specific for cav-1 can be used in an orthotopic mouse model for prostate cancer to suppress tumor growth and metastatic spread. The inhibition of prostate cancer with systemic antibody therapy alone or possibly with other modalities such as chemotherapy may ultimately be of great importance in successfully treating metastatic prostate cancer.
- Medicine and Medical Research