Elucidation of the Molecular Mechanisms Underlying Lymph Node Metastasis in Prostate Cancer
Abstract
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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2005
- Accession Number
- ADA456000
Entities
People
- Kaustubh Datta
Organizations
- Mayo Clinic