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You searched for +publisher:"University of North Carolina" +contributor:("Hamilton, Kathryn Elizabeth"). One record found.

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University of North Carolina

1. Hamilton, Kathryn Elizabeth. Role of suppressor of cytokine signaling 3 in colorectal cancer.

Degree: Cell Biology and Physiology, 2010, University of North Carolina

Patients with inflammatory bowel diseases (IBD) have an increased lifetime risk of developing colorectal cancer (CRC). Suppressors of cytokine signaling (SOCS) are intracellular proteins that provide negative feedback on pro-inflammatory cytokine signaling. SOCS3 silencing in intestinal epithelial cells has previously been shown to promote tumorigenesis in the azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model of inflammation-associated CRC. Mechanisms associated with this effect were increased activation of signal transducer and activator of transcription 3 (STAT3) and NF[kappa]B, and increased expression of TNF[alpha] receptor 2 (TNFR2). TNFR2 is increased in IBD and CRC, but how this receptor is regulated remains undefined. Studies in this dissertation tested the hypothesis that TNFR2 is induced by STAT3 and/or NF[kappa]B pathways, that SOCS3 limits TNFR2 expression, and that SOCS3 is a tumor suppressor in both sporadic and inflammation-associated cancer. Colon cancer cell lines were treated with IL-6 and TNF[alpha] in the presence of STAT3 or NF[kappa]B inhibitors. STAT3 inhibition dramatically decreased cytokine-induction of TNFR2, implicating STAT3 as a critical mediator of TNFR2 induction. SOCS3 limited cytokine-induction of TNFR2, as well as STAT3 binding to consensus sequences within the TNFR2 promoter. SOCS3 also limited TNFR2-mediated proliferation and anchorage-independent growth of colon cancer cells. Together these findings support the concept that SOCS3 exerts a tumor suppressor role in part by limiting the growth-promoting abilities of TNFR2. To test the whether low SOCS3 expression predicts risk of early stage CRC, biopsies of normal mucosa from colonoscopy patients with and without adenomas were assayed for SOCS3 mRNA. No significant difference in SOCS3 mRNA was observed in normal mucosa of patients with and without adenoma. Thus SOCS3 silencing in normal mucosa does not predict adenoma risk. To test whether SOCS3 normally limits tumorigenesis in sporadic CRC, mice with IEC-SOCS3 silencing were subjected to the AOM model of spontaneous, non-inflammatory CRC. Mice with SOCS3 silencing exhibited a 75% increase in colon tumor incidence. Collectively, these data indicate that SOCS3 normally modulates multiple pro-tumorigenic pathways that contribute to both inflammation-associated and sporadic CRC. Advisors/Committee Members: Hamilton, Kathryn Elizabeth, Lund, Pauline Kay.

Subjects/Keywords: School of Medicine; Department of Cell Biology and Physiology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Hamilton, K. E. (2010). Role of suppressor of cytokine signaling 3 in colorectal cancer. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:095fdc60-260b-46ee-81c2-299f00899349

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Hamilton, Kathryn Elizabeth. “Role of suppressor of cytokine signaling 3 in colorectal cancer.” 2010. Thesis, University of North Carolina. Accessed October 27, 2020. https://cdr.lib.unc.edu/record/uuid:095fdc60-260b-46ee-81c2-299f00899349.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Hamilton, Kathryn Elizabeth. “Role of suppressor of cytokine signaling 3 in colorectal cancer.” 2010. Web. 27 Oct 2020.

Vancouver:

Hamilton KE. Role of suppressor of cytokine signaling 3 in colorectal cancer. [Internet] [Thesis]. University of North Carolina; 2010. [cited 2020 Oct 27]. Available from: https://cdr.lib.unc.edu/record/uuid:095fdc60-260b-46ee-81c2-299f00899349.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hamilton KE. Role of suppressor of cytokine signaling 3 in colorectal cancer. [Thesis]. University of North Carolina; 2010. Available from: https://cdr.lib.unc.edu/record/uuid:095fdc60-260b-46ee-81c2-299f00899349

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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