Aberrant Chromatin Modification as a Mechanism of Prostate Cancer Progression
Abstract
Progression of prostate cancer (PCa) from hormone-dependent to hormone-refractory state represents one of the major hurdles in the successful treatment of cancer patients. Early studies showed that nearly all cancers retain androgen receptor (AR) -mediated signaling pathway. One of the working models has been that shifts from paracrine to autocrine expression of growth factors and abnormal function of their receptors contributes to the progression to androgen-independent cancer through modulating the function of AR. We proposed a new hypothesis that chromatin histone modification and remodeling could be a key step in PCa progression. The purpose of this study is to test this new hypothesis. We proposed to identify altered histone modification patterns linked to progression of prostate cancer and then identify the enzymatic activities that are responsible for the alteration. The cope of this study is to first analyze histone acetylation and phosphorylation patterns on androgen receptor (AR) target genes such as PSA and other genes important for cell proliferation in malignant prostate cancer cells at different stages as well as normal prostate epithelial cells. Comparison of the patterns of histone modifications between these cells will allow us to identify the chromatin modifications that are altered during the progression of prostate cancer. Identification of specific changes in hi stone modifications between normal and cancer cells will then help identify the responsible enzymatic activities.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA407398
Entities
People
- Hongwu Chen
Organizations
- University of California