Defense Date

2013

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology

First Advisor

W. Andrew Yeudall

Abstract

Head and neck squamous cell carcinoma (HNSCC) is one of the ten most common cancers worldwide, with a survival rate of less than 50%. A class of mutant p53, known as gain of function (GOF) mutant p53, has been found to be expressed in tumors in these patients. GOF mutant p53 not only loses the wild type tumor suppressor functions, but also gains aberrant functions that have been linked to tumorigenesis. In this current study, we utilized a model system consisting of cells derived from HNSCC tumors in order to investigate our hypothesis that GOF mutant p53 enhances, and p63 inhibits, EPS8 and CXCL5 expression and promoter activity. We found decreased EPS8 expression, CXCL5 expression, and cellular migration associated with the loss of GOF mutant p53. This indicates an enhancing role of GOF mutant p53 in cellular migration and expression of these target genes. The loss of GOF mutant p53 was also associated with decreased EPS8 and CXCL5 promoter activity, indicating upregulation of these target gene promoters by GOF mutant p53. We found increased EPS8 expression,CXCL5 expression, and cellular migration with the loss of p63 in cell expressing high levels of p63. This indicates an ixinhibitory role of p63 on the expression of these target genes and cellular migration. Loss of p63 was also associated with increased EPS8 and CXCL5 promoter activity, indicating p63 may be downregulating these target gene promoters. Based on our knowledge of EPS8 and CXCL5 in tumorigenesis, our findings suggest that GOF mutant p53 and p63 play opposing rolesin HNSCC tumorigenesis. Additional studies are needed to further elucidate the mechanism by which GOF mutant p53 and p63 regulate EPS8 and CXCL5 expression and promoter activity.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

August 2013

Available for download on Tuesday, August 14, 2018

Included in

Physiology Commons

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