Abstract A15: Using genetic and pharmacological methods to explore role of the methyltransferase Ezh2 in mouse mammary tumorigenesis

ErbB2 (HER2/Neu) is a receptor tyrosine kinase over expressed in 20-30% of primary human breast cancer cancer, and correlated with poor clinical outcome. However, the mechanisms through which ErbB2 contributes to tumorigenesis and poor patients prognosis is unclear. Over the last decade, several lines of evidence have demonstrated that the transformation of a normal epithelial cells to a malignant phenotype requires the accumulation of multiple genetics and epigenetic events, including post translational modifications of histones. Enhancer of Zeste 2 (Ezh2) is a polycomb group protein that, as a part of the PRC2 complex mediates gene silencing through tri-methylation of lysine 27 on histone 3 (H3K27me3). Interestingly, several clinical studies have reported EZH2 transcript and protein levels to be elevated in aggressive human breast carcinomas.To investigate the requirement of Ezh2 in mouse mammary epithelial tumour initiation, we have crossed an Ezh2 conditional knock out mouse strain to a tetracycline inducible mammary epithelium specific Polyoma virus Middle T (PyVmT) transgenic mouse strain. The PyVmT model provides insight into how active receptor tyrosine kinase signalling can direct cellular transformation and its benefits include rapid tumour onset and well characterized disease progression, while the tetracycline-inducible systems allows for bypassing any developmental defects in the mammary gland due to Ezh2 ablation. Tumour onset in Ezh2 deficient mice are delayed(...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Animal Models: Poster Presentations - Proffered Abstracts Source Type: research