Abstract LB-389: The function of histone demethylase RBP2 in breast cancer metastasis and drug resistance

Metastasis and drug resistance are two major challenges in cancer therapies. The occurrence of these two events requires cancer cells to gain new mutations or change their expression profiling, or both, adapt to new environment (i.e. distal organs or drug treatments). These changes likely follow Darwin's evolutionary theory: heterogeneous of cancer cells are generated randomly and more aggressive cells are selected by the tissue environment. Stable inheritance of genome and epigenetic states could delay metastasis and drug resistance. Trimethylated lysine 4 in histone H3 (H3K4me3) is the epigenetic marker for transcriptionally active promoters and the binding site for transcriptional activators. Removing the methyl groups from trimethylated H3K4 on gene promoter regions is a common epigenetic strategy for gene silencing. The JARID1 family members are to date the only known proteins responsible for catalyzing demethylation of trimethylated H3K4. Therefore they are essential in cell differentiation and development. Even though JARID1A (RBP2) was implicated in tumorigenesis of certain cancer types, its exact roles are still poorly understood. I hypothesized that RBP2 contributes to changes of epigenetic states during the occurrence of metastasis and drug resistance. Consistent with my hypothesis, I found that RBP2 is highly expressed in metastatic breast cancer cells and Herceptin tolerant population. Loss of RBP2 decreased lung metastatic gene signature and increase drug sensitivity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-389. doi:1538-7445.AM2012-LB-389