nsforming Properties of 8p11-12 Amplified Genes in R an Breast Cancer

nloaded plification of the 8p11-12 region has been found in about 15% of human breast cancers and is associated oor prognosis. Earlier, we used genomic analysis of copy number and gene expression to perform a d analysis of the 8p11-12 amplicon to identify candidate oncogenes in breast cancer. We identified didate genes and provided evidence that three genes, namely, LSM-1, TC-1, and BAG4, have transforming ties when overexpressed. In the present study, we systematically investigated the transforming proper13 newly identified 8p11-12 candidate oncogenes in vitro. WHSC1L1, DDHD2, and ERLIN2 were most ly transforming oncogenes based on the number of altered phenotypes expressed by the cells. WHSC1L1 ns a PWWP-domain that is a methyl-lysine recognition motif involved in histone code modification and etic regulation of gene expression. Knockdown of WHSC1L1 in 8p11-12–amplified breast cancer cells d in profound loss of growth and survival of these cells. Further, we identified several WHSC1L1 target resulte genes, one of which is iroquois homeobox 3 gene (IRX3), a member of the Iroquois homeobox transcription factor family. Cancer Res; 70(21); 8487–97. ©2010 AACR.