Abstract IA16: Breaking the balance between E2F activators and atypical repressors: Consequences to development and cancer

E2F transcriptional activators and repressors regulate cell cycle-dependent gene expression. Using a series of loss- and gain-of-function alleles to dial E2F transcriptional output we show that mouse development is relatively insensitive to alterations in E2F levels and composition. However, modest increases in E2F output resulted in spontaneous hepatocellular carcinoma (HCC) without additional organ involvement, whereas decreases protected against HCC. Cell type- and temporal-specific gene ablation strategies defined a cell-autonomous oncogenic role for E2F1/3B and a tumor suppressor role for E2F7/8 in hepatocytes. Genetic, biochemical and profiling studies suggest a mechanism involving E2F1/3B-mediated activation and E2F7/8-mediated repression of a common set of targets during early post-natal liver development, which are associated with HCC progression. Thus, while overall development is sufficiently robust, the liver is uniquely sensitive to perturbations in E2Fs. In summary, we identified the critical network components in immature hepatocytes that control E2F output and foster a cancer-free life span.Citation Format: Gustavo W. Leone. Breaking the balance between E2F activators and atypical repressors: Consequences to development and cancer. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Cancer Cell Cycle - Tumor Progression and Therapeutic Response; Feb 28-Mar 2, 2016; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(11_Suppl):Abstract n...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: E2F Family Functions: Alterations and Consequences: Oral Presentations - Invited Abstracts Source Type: research