Regulation of the Human MYC Proximal Promoter by STAT Proteins in Cancer Cells
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Author(s)
Primary Supervisor
Ralph, Stephen
Other Supervisors
Neuzil, Jiri
Year published
2011
Metadata
Show full item recordAbstract
Accumulating evidence has indicated important roles played by Signal Transducer and Activator of Transcription (STAT) molecules, STAT1, STAT3 and STAT5 in the abnormal growth of cancer cells. Associated with these malignant changes, many of the STAT-target genes involved in cell growth regulation also become deregulated in cancer cells. One very important oncogene overexpressed in many cancers is MYC whose gene promoter has previously been found to be STAT regulated. Gene reporter assays provide useful tools for studying the roles of cytokines such as interferon (IFN) and their activation of STAT-dependent promoters. The ...
View more >Accumulating evidence has indicated important roles played by Signal Transducer and Activator of Transcription (STAT) molecules, STAT1, STAT3 and STAT5 in the abnormal growth of cancer cells. Associated with these malignant changes, many of the STAT-target genes involved in cell growth regulation also become deregulated in cancer cells. One very important oncogene overexpressed in many cancers is MYC whose gene promoter has previously been found to be STAT regulated. Gene reporter assays provide useful tools for studying the roles of cytokines such as interferon (IFN) and their activation of STAT-dependent promoters. The aims of this study were to: 1) establish luciferase reporter vectors for evaluating STAT-mediated gene regulation; 2) investigate the differential DNA binding of STAT1 versus STAT3 and their sequence recognition and relate this to the regulation of key genes involved in malignancy, such as MYC; and 3) investigate the role of STAT5 in the regulation of the MYC promoter, given preliminary data which indicated STAT5 might be directly involved.
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View more >Accumulating evidence has indicated important roles played by Signal Transducer and Activator of Transcription (STAT) molecules, STAT1, STAT3 and STAT5 in the abnormal growth of cancer cells. Associated with these malignant changes, many of the STAT-target genes involved in cell growth regulation also become deregulated in cancer cells. One very important oncogene overexpressed in many cancers is MYC whose gene promoter has previously been found to be STAT regulated. Gene reporter assays provide useful tools for studying the roles of cytokines such as interferon (IFN) and their activation of STAT-dependent promoters. The aims of this study were to: 1) establish luciferase reporter vectors for evaluating STAT-mediated gene regulation; 2) investigate the differential DNA binding of STAT1 versus STAT3 and their sequence recognition and relate this to the regulation of key genes involved in malignancy, such as MYC; and 3) investigate the role of STAT5 in the regulation of the MYC promoter, given preliminary data which indicated STAT5 might be directly involved.
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Thesis Type
Thesis (PhD Doctorate)
Degree Program
Doctor of Philosophy (PhD)
School
School of Medical Science
Copyright Statement
The author owns the copyright in this thesis, unless stated otherwise.
Item Access Status
Public
Note
The Appendices have not been published here.
Subject
Signal Transducer and Activator of Transcription (STAT) molecules
Cancer cells
Human MYC Proximal Promoter
STAT-mediated gene regulation