Histone Code Modulation by Oncogenic PWWP-Domain Protein in Breast Cancers
Abstract
Amplification of 8p11-12 occurs in approximately 15% of human breast cancer (HBC), and this region of amplification is significantly associated with disease-specific survival and distant recurrence in breast cancer patients. Earlier, we used genomic analysis of copy number and gene expression to perform a detailed analysis of the 8p11-12 amplicon for identifying candidate oncogenes in breast cancer. We identified Wolf-Hirschhorn syndrome candidate 1-like 1 (WHSC1L1) as a candidate oncogene based on statistical analysis of copy number increase and over expression. In this study, we demonstrated that knockdown of this gene in WHSC1L1 amplified breast cancer cells resulted in profound loss of growth and survival potential. WHSC1L1 contains a PWWP-domain that is a methyl-lysine recognition motif involved in histone code modification and epigenetic regulation of gene expression. To identify genes that may be altered in their expression by over expression of WHSC1L1, we performed expression profiling and identified genes including UHRF1 with altered expression upon WHSC1L1 knockdown in breast cancer cells. We will continue to investigate how WHSC1L1 contributes to transformation through the alternation of epigenetic histone marks and acquisition of stem cell-like properties in breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2011
- Accession Number
- ADA547592
Entities
People
- Zeng-quan Yang
Organizations
- Wayne State University