Isolation of Genes Involved in Human Prostate Cancer Progression by Functional Expression Cloning
Abstract
During the first year of this award, we have made great progress toward defining the molecular basis for androgen independent prostate cancer progression. A key theme from our findings is the concept that genes which cause androgen independence can do so by activating the androgen receptor in a ligand-independent fashion, Several lines of evidence from our work support this hypothesis. We have identified two genes - the Her2/neu receptor tyrosine kinase and the serine/threonine kinase MEKKl - which can activate the androgen receptor and have major effects on prostate cancer growth. In the case of Her2/neu, the availability of drugs which can attack the Her2/neu protein raise the possibility of clinical trials to address the role of this gene in human prostate cancer. We have also isolated a third gene, encoding the serine protease cathepsin D (unpublished data), which confers androgen independent growth in prostate cancer cells in SCID mouse models. Current work is focused on developing transgenic mouse models of prostate cancer based on these genes. Specifically, we have generated several founder lines expressing cathepsin D under the control of the prostate- specific probasin promoter and are in the process of characterizing this phenotype. These mice should lead to newer mouse models and will allow us to define the role of this protease in prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA380403
Entities
People
- Charles Sawyers
Organizations
- University of California, Los Angeles