Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/135192
Title: INVESTIGATION OF TGF-??ASSOCIATED MASTER-LIKE TRANSCRIPTION FACTORS IN BREAST CANCER
Authors: ZHANG SITING
Keywords: TGF-β signaling, Breast cancer, Master transcription factor, E2F1, Super-enhancer, ChIP-seq
Issue Date: 21-Feb-2017
Source: ZHANG SITING (2017-02-21). INVESTIGATION OF TGF-??ASSOCIATED MASTER-LIKE TRANSCRIPTION FACTORS IN BREAST CANCER. ScholarBank@NUS Repository.
Abstract: Transforming growth factor β (TGF-β) signaling is important in early development, lineage specification, and tumorigenesis. In cancer, TGF-β can function as either a tumor suppressor or a tumor promoter at different stages of carcinogenesis. In early development, the context specificity of TGF-β signaling is partially determined by master transcription factors guiding SMAD-dependent genomic regulation. We hypothesize that a similar role for “master-like transcription factors” may determine context-specific genomic regulation of TGF-β signaling in tumorigenesis. We address this problem through integrative genomic studies and bioinformatics analysis of TGF-β-responsive breast cancer cell models, as well as data from TCGA. We identify a context-specific interaction between E2F Transcription Factor 1 (E2F1) and SMAD-dependent signaling in MCF7, an ER-positive luminal-A breast cancer model. E2F1 is a potential master-like transcription factor in this setting: it is not required for SMAD3 binding, but co-occupies genomic sites with SMAD3 and coordinates with SMAD3 to regulate downstream genes. Moreover, 138 putative super-enhancers were found in response to TGF-β in MCF7, whose associated genes were enriched in ten oncogenic gene sets including RB-mediated oncogenes and TGF-β mediated oncogenes.
URI: http://scholarbank.nus.edu.sg/handle/10635/135192
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