Histone Code Modulation by Oncogenic PWWP-Domain Protein in Breast Cancers
Abstract
Earlier, we used genomic analysis of copy number and gene expression to perform a detailed analysis of the 8p11-12 amplicon to identify candidate oncogenes in breast cancer. We identified 21 candidate genes and provided evidence that three genes; LSM-1, TC-1 and BAG4 have transforming properties when over expressed. Recently, we systematically investigated the transforming properties of thirteen newly identified 8p11-12 candidate oncogenes in vitro. We found that WHSC1L1, DDHD2 and ERLIN2 are the most potently transforming oncogenes we tested from the 8p11-12 region based on the number of altered phenotypes expressed by the cells. WHSC1L1 contains a PWWP-domain that is a methyl-lysine recognition motif involved in histone code modification and epigenetic regulation of gene expression. Knockdown of WHSC1L1 in 8p11-12 amplified breast cancer cells resulted in profound loss of growth and survival of these cells. Further, we identified several WHSC1L1 target genes, one of which is iroquois homeobox 3 gene (IRX3), a member of the Iroquois homeobox transcription factor family.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2010
- Accession Number
- ADA547591
Entities
People
- Zeng-quan Yang
Organizations
- Wayne State University