Date of Award
Spring 2026
Abstract
Approximately 13% of women are diagnosed with breast cancer and it’s the second leading cancer-related cause of death among women. Signal transducer and activator of transcription 3 (STAT) and STAT5 are two related transcription factors that are highly involved in breast cancer. Since STAT5 is associated with more favorable patient outcomes and STAT3 is associated with aggressive tumors, we sought to understand the mechanisms underlying the distinct transcriptional programs driving these differences in tumor behaviors. First, we explored how STAT5 can be used to modulate STAT3 and aggressive tumor characteristics. We demonstrated that co-activation of STAT3 and STAT5 in patient breast cancer samples was associated with reduced epithelial-mesenchymal transition and other aggressive phenotypes. Next, we created a constitutively active STAT5 cell line to characterize how constitutive STAT5 can modulate the aggressive phenotypes of triple negative breast cancer. We then characterized the binding profiles of STAT3 and STAT5 to better understand how concurrent activation of STAT3 and STAT5 in breast cancer tumors is associated with a more favorable prognosis compared to activation of STAT3 alone. We identified 110 overlapping binding sites and demonstrated distinct expression patterns of the associated genes based on subtype and inferred STAT transcriptional activity. We also performed a motif enrichment analysis and identified TEAD4 as a potential modulator of transcription for STAT3 and STAT5. Lastly, we characterized how 3D growth influences the transcriptional activity of STAT3 and STAT5 in breast cancer. We revealed that STAT3 DNA binding is increased with 3D growth and that competition between STAT3 and STAT5 binding for a well-characterized binding site is altered in 3D-grown cells. These studied highlight the importance of understanding the relationship between STAT3 and STAT5 activity in breast cancer.
Document Type
Dissertation
First Advisor
Sarah Walker
Second Advisor
Vicki Jeffers
Third Advisor
W. Kelley Thomas
Department or Program
Biochemistry
Degree Name
Doctor of Philosophy
Recommended Citation
Temple, Alexandra Elizabeth, "Characterizing the Relationship Between STAT3 and STAT5 in Breast Cancer" (2026). Doctoral Dissertations. 3015.
https://scholars.unh.edu/dissertation/3015