Biochemistry, Biophysics, and Structural Biology Commons^™

Mechanisms For Survival And Drug Resistance In Cancer Cells, Matthew B. Utter

Dissertations, Theses, and Capstone Projects

PART I

Prostate cells are hormonally driven to grow and divide. Typical treatments for prostate cancer involve blocking the hormone androgen from activating the androgen receptor (AR) and thus inhibit growth and proliferation of the cancer. Androgen deprivation therapy (ADT) can lead to the selection of cancer cells that grow and divide independently of androgen receptor activation. Prostate cancer cells that are insensitive to androgens commonly display metastatic phenotypes and reduced long-term survival of patients. In this study, we provide evidence that androgen-insensitive prostate cancer cells have elevated phospholipase D (PLD) activity relative to the androgen-sensitive prostate cancer cells. PLD …

Identification And Characterization Of Protein Phopshatases Regulating The Sma/Mab Pathway In C. Elegans, Sheng Xiong

Dissertations, Theses, and Capstone Projects

TGF-beta signaling is a conserved signaling pathway among eukaryotes, which controls various normal cellular responses from cell proliferation to cell death. The mutations in its components are found in developmental disorders and cancer. Therefore, this signaling pathway is extensively investigated so that new therapeutic targets could be discovered and novel drugs could be developed. Previous studies suggested the involvement of phosphatases in regulation of TGF-beta signaling, but these studies were performed in cell culture rather than intact organisms. C. elegans is a tractable organism in which to study signaling in vivo. In C. elegans, growth is controled by a conserved …

Modulation Of Tgfβ-Induced Pai -1 Expression By Changes In Actin Polymerization In Human Mesangial Cells, Keyur Patel

Theses and Dissertations in Biomedical Sciences

Chronic renal diseases show increased deposition of extracellular matrix (ECM) in the glomerulus (glomerulosclerosis). Glomerulosclerosis is associated with activation of normally quiescent glomerular mesangial cells into myofibroblast-like cells. The overall objective of this study is to delineate cellular mechanism/s of myofibroblast-differentiation in disease states. In cultured mesangial cells certain characteristics of myofibroblast differentiation (α-smooth muscle actin (α-SMA) and hypertrophy) are associated with an increase in polymeric actin microfilaments (stress fibers). It is likely that other genes are also regulated in an actin cytoskeleton-dependent manner during myofibroblast differentiation. In these studies, we therefore examined the hypothesis that changes in the actin …