Abstract A57: The novel function of nuclear ErbB-2 in regulating transcription of rRNA genes

Abstract

Accumulating evidence shows that deregulation of ribosomal RNA (rRNA) synthesis and translation control can facilitate tumorigenesis. The ErbB2 growth factor receptor is overexpressed in many human tumors and has been detected in the nucleus, but the role of nuclear ErbB2 is obscure. Here, we demonstrated a novel function of nuclear ErbB2 in enhancing rRNA gene transcription by RNA polymerase-l (RNA Pol I). Nuclear ErbB2 physically associates with β-actin and RNA Pol I, coinciding with active RNA Pol I transcription sites in nucleoli. RNAi-mediated knockdown of ErbB2 reduced pre-rRNA and protein synthesis. In contrast, wild-type ErbB2 augmented pre-rRNA level, protein production and cell size/cell growth, but not by an ErbB2 mutant which is defective in nuclear translocation. Chromatin immunoprecipitation assays revealed that ErbB2 enhances binding of RNA Pol I to rDNA. Additionally, ErbB2 associated with rDNA, RNA Pol I, and β-actin, suggesting how it could stimulate rRNA production, protein synthesis, and increased cell size and cell growth. Lastly, ErbB2-potentiated RNA Pol I transcription could be stimulated by ligand and was not substantially repressed by inhibition of PI3-K and MEK/ERK, the main ErbB2 effector signaling pathways. Together, our findings indicate that nuclear ErbB2 functions as a regulator of rRNA synthesis and cellular translation, which may contribute to tumor development and progression. This work was supported by National Health Research Institutes NHRI-EX100-9603BC, National Science Council NSC95-2311-B-039-002 and NSC99-3111-B-039-001 and Department of Health DOH99-TD-I-111-TM026 and DOH100-TD-C-111-005 (to LYL), Taiwan. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A57.