Functional Genomics to Identify Therapeutic Targets in Cancer Stem Cells Using a Novel Murine CRPC Model
Abstract
Prostate cancer is the most common noncutaneous malignancy in men in the United States1. Prostate cancer after Androgen deprivation therapy (ADT) will invariably become refractory to castration, resulting in the development of lethal castration resistant prostate cancer (CRPC), which remains incurable. It is generally believed that prostate stem cells can be the cell of origin for prostate cancers accounting for the development of CRPC, but the identity of prostate cancer stem cells in CRPC remains elusive. Here I used a metastatic Ptenpc-/- Smad4pc-/- mouse prostate cancer model to study the mechanisms for CRPC and the biology of cancer stem cells. As compared to Ptenpc-/- tumors, I discovered that Ptenpc-/-Smad4pc-/- tumors are resistant to ADT, showed both basal and luminal phenotypes with increased proliferation. Furthermore, ADT in Pten(pc)-/-Smad4(pc)-/- mice may promote massive lung metastasis. Interestingly, by integrative analysis of microarray datasets I identified pathways that may play a role in the resistance to ADT and cancer stem cells, including the Rb/E2Fs and Yap1, which will be subjected to functional validation in vitro and in vivo. Thus our metastatic mouse prostate cancer model will facilitate the process of identifying novel therapeutic targets for CRPC using a functional genomics approach.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2014
- Accession Number
- ADA631924
Entities
People
- Guocan Wang
Organizations
- The University of Texas MD Anderson Cancer Center