Histone Code Modulation by Oncogenic PWWP-domain Protein in Breast Cancers

摘要: Abstract : Amplification of 8p11-12 occurs in approximately 15% human breast cancer (HBC), and this region amplification is significantly associated with disease-specific survival distant recurrence patients. Earlier, we identified Wolf-Hirschhorn syndrome candidate 1-like 1 (WHSC1L1) as a oncogene amplified region, based on statistical analysis copy number increase overexpression. In study, demonstrated that WHSC1L1 acts transforming gene: stable overexpression nontumorigenic MCF10A cells induces transformed phenotypes, whereas knockdown 8p12 amplified, ER-positive inhibits proliferation vitro. We also found likely the acquisition stem cell-like properties family proteins have been shown to bind methylated histones, specifically H3K36 methylation marks. determined global levels panel cell lines, including WHSC1L1-amplified SUM-44 SUM-52 lines. several target genes, one which Iroquois homeobox 3 gene, member transcription factor family. summary, our findings provide strong foundation for further mechanistic research therapeutic options using WHSC1L inhibitors treat cancer.