Eva Sahakian

Abstract

A defining characteristic of solid tumors is the capacity to divide and spread under conditions of nutrient deprivation and limited oxygen availability. These microenvironmental stresses arise from structural abnormalities in tumor vessels that lead to aberrant microcirculation. Hypoxia acts as a physiological “selection pressure” in the progression of cancer by activating pathways and enhancing the expression of specific genes in tumor cells which eventually diminish their apoptotic potential. Ultimately, hypoxic microenvironment functions as a “stress factor”, selecting cells with the ability to survive and divide under anoxic conditions. The members of the PIM family of cytoplasmic serine threonine kinases are true oncogenes that function as survival factors in response to many stresses. We have previously reported that PIM1 is upregulated during cytotoxic drug-induced stress and improves survival of PCa cell lines.

In this study we hypothesized that the activation of HIF-1α and STAT3 in hypoxia up-regulates the expression the PIM1 kinase, ultimately mediating chemoresistance and cell survival through hypoxia-induced stress tolerance in PCa.

LLU Discipline

Microbiology and Molecular Genetics

School

Graduate Studies

First Advisor

Michael B. Lilly

Second Advisor

Carlos A. Casiano

Third Advisor

Tom Linkhart

Fourth Advisor

Marvin Payne

Fifth Advisor

Nathan R. Wall

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

2010

Date (Title Page)

6-2010

Language

English

Library of Congress/MESH Subject Headings

Prostatic Neoplasms -- genetics; Prostatic Neoplasms -- microbiology; Moloney murine leukemia virus; Virus Integration; Cell Line, Tumor; Hypoxia-Inducible Factor 1.; Reactive Oxygen Species -- metabolism; Gene Expression

Type

Dissertation

Page Count

xiv; 153

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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