Date

January 2007

Document Type

Dissertation

Degree Name

Ph.D.

Department

Dept. of Molecular Microbiology and Immunology

Institution

Oregon Health & Science University

Abstract

This dissertation discusses novel findings of the insulin-like growth factor system and cathepsin B in the context of Kaposi sarcoma-associated herpesvirus (KSHV)induced tumorigenesis. To study KSHV -induced tumorigenesis, a tissue culture model system developed by Ashlee Moses was used, which best resembles in vivo conditions. Using a global approach of transcription profiling, KSHV-infected and uninfected E6/E7- immortalized dermal microvascular endothelial cells were compared by microarray to discern what cellular genes are involved in KSHV -mediated tumorigenesis. Within the insulin-like growth factor system, IGFBP-1, -2, -6, the insulin receptor and the insulin-like growth factor II receptor were identified as having important functions in Kaposi sarcoma. In addition, studies described in this dissertation reveal that the cysteine protease cathepsin B intracellularly regulates tumor invasion. Furthermore, a causal link between the insulin-like growth factor II receptor and cathepsin B was discovered, which proves to be necessary for KSHV -mediated tumorigenesis. These discoveries are the first to be documented for Kaposi sarcoma and present potential new targets for designing anti-cancer therapies.

Identifier

doi:10.6083/M4SB43R1

School

School of Medicine

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