Access Type

Open Access Dissertation

Date of Award

1-1-1998

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Cancer Biology

First Advisor

Dr. Kenneth J. Pienta

Abstract

The nuclear matrix, the RNA-protein skeleton of the nucleus, is known to play functional and structural roles within the cell. My thesis investigated the roles of the nuclear matrix proteins under various circumstances. First, the rat prostate cancer cell line (MLL) was injected into various sites within the rat. Tumors were isolated and nuclear matrix proteins isolated and analyzed by two-dimensional electrophoresis. Upon comparison, distinct nuclear matrix protein differences were observed in all of the organ sites that were investigated suggesting that the extracellular matrix, as well as growth factors and hormones, may be important in directing the production of nuclear matrix proteins. Second, nuclear matrix proteins from various cell lines representing the four classes of human lung carcinoma were analyzed. Upon comparison, it was observed that there were at least two classes of nuclear matrix proteins present. The majority of the nuclear matrix proteins were common within each lung cancer category, while other nuclear matrix proteins were found to be different. These nuclear matrix protein differences may be due to the various classes of phenotypic and genotypic distinct classes of lung cancer. Lastly, several reproducible nuclear matrix proteins isolated from the human breast MCF10A cell line were characterized. Although cDNA library screening proved unsuccessful, antibodies toward one of these proteins (KP3) provided further information into the function of this protein. Western and immunocytochemical analyses provided evidence to suggest that this protein was common and could be found in all cell lines and tissues that were analyzed. In addition, further analyses suggested that this protein could play an important role(s) in mitosis. Multidrug resistance (MDR) was also investigated in various human and rat prostate cancer cell lines. The majority of the cell lines analyzed did express an increased MDR phenotype when compared to the MDR negative controls. Two rat prostate cell lines (MLL and AT3) where selected and grown in increasing concentrations of doxorubicin to enhance the MDR phenomenon. MLL and AT3 MDR cell lines had an increased MDR phenotype when compared to their normal counterparts.

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