GSBS Dissertations and Theses

Approval Date

1-4-2016

Document Type

Master's Thesis

Academic Program

Cancer Biology

Department

Molecular, Cell and Cancer Biology Department

First Thesis Advisor

Arthur Mercurio, PhD

Keywords

Breast Cancer, Integrin alpha6beta4, Neoplastic Stem Cells, Tumor Formation

Subjects

Theses, UMMS; Breast Neoplasms; Integrin alpha6beta4; Neoplastic Stem Cells

Abstract

The integrin α6β4 (referred to as β4) is expressed in epithelial cells where it functions as a laminin receptor. Integrin β4 is important for the organization and maintenance of epithelial architecture in normal cells. Particularly, β4 is shown to be essential for mammary gland development during embryogenesis. Integrin β4 also plays important roles in tumor formation, invasion and metastasis in breast cancer. However, the mechanism of how integrin β4 mediates breast tumor formation has not been settled. A few studies suggest that integrin β4 is involved in cancer stem cells (CSCs), but the mechanism is not clear. To address this problem, I examined the expression of β4 in breast tumors and its potential role involved in regulating CSCs. My data shows that β4 is expressed heterogeneously in breast cancer, and it is not directly expressed in CSCs but associated with a basal epithelial population. This work suggests that β4 can regulate CSCs in a non-cell-autonomous manner through the interactions between β4+ non-CSC population and β4- CSC population. My data also shows that β4 expression is associated with CD24+CD44+ population in breast tumor. To further study the role of β4 in breast cancer progression, I generated a β4 reporter mouse by inserting a p2A-mCherry cassette before ITGB4 stop codon. This reporter mouse can be crossed with breast tumor models to track β4+ population during tumor progression.

DOI

10.13028/M2588G

Rights and Permissions

Copyright is held by the author, with all rights reserved.

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