The Role of the Sonic Hedgehog Pathway for Prostate Cancer Progression
Abstract
The hedgehog pathway plays a critical role in the development of prostate cancer. However the role of the hedgehog pathway in prostate cancer is not clear. In the previous funding period we have reported activation of hedgehog signaling in advanced and metastatic tumors. We also reported one possible molecular mechanism by which activated hedgehog signaling alter cell functions. Here we report another mechanism by which hedgehog signaling is activated in prostate cancer. We found that the Shh promoter activity is elevated in several cancer cell lines with hedgehog signaling activation including LNCaP Huh7 cells. Growth of these cells depends on the presence of ligand sonic hedgehog. Following treatment of neutralizing antibodies to sonic hedgehog we observed reduced cell growth and apoptosis in several cancer cell lines. Through further analyses we narrowed the region responsible for sonic hedgehog promoter activity to a region less than 1 kb. Currently we are trying to identify the transcriptional factors involved in regulation of sonic hedgehog expression. Furthermore we have made some progress in animal models for hedgehog signaling-mediated carcinogenesis. Currently we have established conditioned knockout of Ptch1 (or knock/in of activated SMO) in mice using Keratin 14 promoter which targets not only skin epidermis but also prostate epithelium. These mice will be mated with other genetically engineered mice to obtain bigenic mice in our analysis of prostate carcinogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2007
- Accession Number
- ADA469765
Entities
People
- Jingwu Xie
Organizations
- University of Texas Medical Branch