In the United States, breast cancer is the most common form of non-skin cancer and the second leading cause of cancer related deaths in women. The National Cancer Institute recognizes two clinical challenges in breast cancer research. First, the prevention of breast cancer is seen as a challenge due to the complex nature of the developing breast. Second, there is no effective treatment for the metastatic diseases due to the presence of cancer stem-like cells. Cancer stem-like cells (CSC) have the ability to continuously proliferate and differentiate, sustaining the original tumor and generating new tumors. CSCs represent a small population of a tumor and can be identified by cell surface protein markers that distinguish the cells from the surrounding population of cancer cells. In breast cancer, CSCs can be identified by the up-regulation of CD44, a cell surface glycoprotein, and the down-regulation of CD24, a cell adhesion molecule. CD44 is a cell surface glycoprotein involved in a number of cellular processes, including cell adhesion, migration and cell-cell interactions. The protein is a receptor for hyaluronic acid and it can interact with other ligands such as osteopontin and collagens. Ongoing research of CD44 focuses on downstream effects of CD44 and how variant forms of CD44 function in cancer cells. Despite the intense research aimed at understanding CD44’s role in cancer and cancer stem-like cells, little is known about its regulation in normal or cancer cells. As an important component of gene transcription machinery, cis-regulatory elements are located in non-coding genomic DNA on the same chromosome as the gene of interest and are responsible for the up- and down-regulation of genes. Cis-elements are often highly conserved and tend to be in regions of open chromatin configuration making them accessible to trans-acting factor binding proteins. In this thesis, I have identified a highly conserved region, CR1, with the ability to direct gene expression in a cell specific manner. Further analysis revealed that the trans-acting factor NFκB has the ability to bind CR1 and is involved in regulating CD44 expression. Inhibition of NFκB resulted in reduced CD44 expression and subsequently a reduction in proliferation and invasiveness of breast cancer cells. These findings provide new insight into molecular mechanism underlying CD44 regulation in breast cancer cells and offers new clues to therapeutic targets that may help eliminate chemo- and radiation-resistant cancer cells and subsequent metastasis.
Subject (authority = RUETD)
Topic
Cell and Developmental Biology
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_4979
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xiii, 118 p. : ill.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = vita)
Includes vita
Note (type = statement of responsibility)
by Shannon M. Smith
Subject (authority = ETD-LCSH)
Topic
CD antigens
Subject (authority = ETD-LCSH)
Topic
Breast--Cancer--Research
Subject (authority = ETD-LCSH)
Topic
Cancer cells--Growth--Regulation
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.