Elucidation of the Molecular Mechanisms Underlying Lymph Node Metastasis in Prostate Cancer
Annual rept. 24 Sep 2004-23 Sep 2005
MAYO CLINIC ROCHESTER MN
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Metastatic spread of prostate cancer is the second leading cause of death of men in the United States. Although there are many ways to treat non-metastatic forms of prostate cancer, only androgen-deprivation therapy is available for the later stages of the disease. Again, the cancer will often progress to an androgen-refractory independent, metastatic stage. Recent reports have suggested that the expression of VEGF-C and its receptor VEGFR-3 are directly correlated with lymph node dissemination in prostate cancer. This finding leads one to think that understanding the role of angiogenic molecules like VEGF-C and VEGF-D in molecular detail for lymphatic formation in prostate cancer will provide information on their relationship with lymph node metastasis. The authors have observed up-regulation of VEGF-C in prostate cancer cells upon androgen withdrawal. Down regulation of the IGF-IR pathway and SIRT-1 mediated activation of fork head transcription factor FOXO-1 was the key regulatory mechanism identified for the androgen-dependent regulation of VEGF-C. The authors also have established the orthotopic mouse model of prostate cancer for future studies proposed in this grant.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research