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Investigation of TGF-beta Associated Master-Like Transcription Factors in Breast Cancer.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Investigation of TGF-beta Associated Master-Like Transcription Factors in Breast Cancer./
Author:	Zhang, Siting.
Description:	1 online resource (156 pages)
Notes:	Source: Dissertation Abstracts International, Volume: 76-11C.
Contained By:	Dissertation Abstracts International76-11C.
Subject:	Molecular biology. -
Online resource:	click for full text (PQDT)

Investigation of TGF-beta Associated Master-Like Transcription Factors in Breast Cancer.
Zhang, Siting.

Investigation of TGF-beta Associated Master-Like Transcription Factors in Breast Cancer. - 1 online resource (156 pages)

Source: Dissertation Abstracts International, Volume: 76-11C.

Thesis (Ph.D.)--National University of Singapore (Singapore), 2016.

Includes bibliographical references

Transforming growth factor beta (TGF-beta) signaling is important in early development, lineage specification, and tumorigenesis. In cancer, TGF-beta can function as either a tumor suppressor or a tumor promoter at different stages of carcinogenesis. In early development, the context specificity of TGF-beta 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-beta signaling in tumorigenesis. We address this problem through integrative genomic studies and bioinformatics analysis of TGF-beta-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-beta in MCF7, whose associated genes were enriched in ten oncogenic gene sets including RB-mediated oncogenes and TGF-beta mediated oncogenes.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018

Mode of access: World Wide Web

Subjects--Topical Terms:

583443
Molecular biology.
Index Terms--Genre/Form:

554714
Electronic books.

Investigation of TGF-beta Associated Master-Like Transcription Factors in Breast Cancer.
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502 $a Thesis (Ph.D.)--National University of Singapore (Singapore), 2016.
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520 $a Transforming growth factor beta (TGF-beta) signaling is important in early development, lineage specification, and tumorigenesis. In cancer, TGF-beta can function as either a tumor suppressor or a tumor promoter at different stages of carcinogenesis. In early development, the context specificity of TGF-beta 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-beta signaling in tumorigenesis. We address this problem through integrative genomic studies and bioinformatics analysis of TGF-beta-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-beta in MCF7, whose associated genes were enriched in ten oncogenic gene sets including RB-mediated oncogenes and TGF-beta mediated oncogenes.
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