Life Sciences Commons^™

Ezh2 T416 Phosphorylation Enhances Breast Cancer Tumorigenesis, Adam M. Labaff, Adam M. Labaff

Dissertations & Theses (Open Access)

Enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and catalyzes the trimethylation of histone H3 on lysine 27 (H3K27Me3), to repress gene transcription. Many types of cancer stem and progenitor cells, including breast, have demonstrated EZH2 to be fundamental in the biology and promoting the expansion of their cellular populations. How EZH2 regulates each of these respective tumor initiating cells (TICs) populations has been studied, but the signaling transduction mechanisms that regulate EZH2 in these TIC populations is yet to be elucidated. Phosphorylation of EZH2 by cyclin dependent kinases (CDK) has been …

Investigating Potential Bioactive Compounds From Rhodococcus And Their Effects On Mcf7 Breast Cancer Cells, Megan N. Crabtree

Electronic Theses and Dissertations

Many drugs used in the treatment of various cancers are derived from or influenced by compounds from nature. The soil bacterium Rhodococcus is of interest because of its identified secondary metabolic pathways and the production of novel natural antibiotics from several strains. In this study, a solid agar extraction method was used to collect compounds from strains of Rhodococcus. These bacterial compound extracts were then tested using a MTT assay in order to evaluate their effectiveness in augmenting MCF7 breast cancer cell death. The results of two way ANOVA analyses revealed 18 compound extracts from 15 strains of Rhodococcus that …

The Synthesis And Evaluation Of Peptide-Based Probes For The Imaging Of Rhamm Expressing Carcinoma And Glp-1r On Pancreatic Beta Cells, Ashley Esarik

Electronic Thesis and Dissertation Repository

Peptide-based probes are developed into imaging agents to target two different receptors: receptor for HA mediated motility (RHAMM) and glucagon-like peptide 1 receptor (GLP-1R).

In the first project, peptides are derived from tubulin and mimic HA (hyaluronan), the natural ligand of RHAMM. In order to develop the lead candidate peptides into imaging agents, a DOTA chelator which can coordinate a radiometal was coupled onto the lead peptides. Gallium labelling studies were performed and the labelled probes were used in in vivo mouse studies. Various analogues of two of the candidate peptides were also synthesized using bioisosteric, unnatural as well as …

Hcmv Promotes Breast Cancer Metastasis: Impacts Of Cmvil-10 In The Tumor Microenvironment, Robin Bishop

Master's Theses

Human cytomegalovirus (HCMV) is a highly species-specific, common human pathogen. While a large majority of people are infected with HCMV worldwide, infection is typically asymptomatic in immune competent individuals. To enhance virus persistence and avoid immune detection by the host, HCMV exploits the strategy of encoding homologs of cellular cytokines. One factor produced by HCMV-infected cells is the viral cytokine cmvIL-10, which acts through the cellular IL-10 receptor to induce downstream cell signaling. In instances where HCMV-infected cells infiltrate the tumor microenvironment, the presence of cmvIL-10 in may initiate events that promote a more invasive tumor phenotype. Cancer cells that …

Proteomic And Biochemical Studies Of Estrogen-Mediated Signaling And Novel Estrogen Receptor-Interacting Proteins In Breast Cancer Cells, Zhenqi Zhou

Graduate Theses and Dissertations

Estrogen plays essential roles in the growth, development, and homeostasis of a number of tissues, and can also be linked to the growth of breast cancer. The biological activities of estrogen are mediated by estrogen receptors (ERs) ERá and ERâ, and also orphan G-protein-coupled receptor 30 (GPR30). In order to identify novel proteins that are involved in ER-mediated actions of estrogen, we used mass spectrometry-based quantitative proteomic methods to systematically profile global protein expression in responses to E2 (17â-estradiol) stimulation in human breast cancer cell, and identify and characterize cellular novel proteins that are associated with ERs in breast cancer …

A Novel Role Of Oncostatin M In Invasive Breast Cancer: Induction Of Cathepsin D And Lysosomal Trafficking, Jordan Barrie Koncinsky

Boise State University Theses and Dissertations

Oncostatin M (OSM) is an interleukin-6 (IL-6) family cytokine shown to be important in inflammation, hematopoiesis, development and bone homeostasis. Despite its role as a growth suppressor for many cancers, including breast cancer, OSM is currently being studied for its ability to promote tumor invasion and metastasis. Cathepsin D (CTSD) is a lysosomal protease found to be overexpressed and hypersecreted in breast and other cancers. In this study, we found OSM to induce the expression of CTSD protein in human breast cancer cells via the STAT3 and JNK2 pathways. Next, we investigated mechanisms resulting in the increased secretion of CTSD …

Interaction Between Brk And Her2 In Breast Cancer, Midan Ai

Dissertations & Theses (Open Access)

INTERACTION BETWEEN BRK AND HER2 IN BREAST CANCER

Midan Ai, Ph.D.

Supervisory Professor: Zhen Fan, M.D.

Breast tumor kinase (Brk) is a nonreceptor protein-tyrosine kinase that is highly expressed in approximately two thirds of breast cancers but is not detectable or is expressed at very low levels in normal mammary epithelium. Brk plays important roles in promoting proliferation, survival, invasion, and metastasis of breast cancer cells, but the mechanism(s) of which remain largely unknown. Recent studies showed that Brk is frequently co-overexpressed with human epidermal growth factor receptor-2 (HER2) and is physically associated with HER2 in breast cancer. The mechanism …

The Role Of Type I Insulin-Like Growth Factor Receptor Signaling In Breast Cancer Brain Metastasis, Sandra M. Saldana

Dissertations & Theses (Open Access)

Brain metastasis is a common cause of mortality in cancer patients. Approximately 20-30% of breast cancer patients acquire brain metastasis, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF- IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that the IGF-IR signaling axis is constitutively active in brain-seeking sublines of breast cancer cells, driving an increase in in vitro metastatic properties. We demonstrate that IGF-IR signaling is activated in an autocrine manner …

A Literature Review Of Risk Factors For The Development Of Breast Cancer: Risks And Prevention Methods, Anna K. Manneschmidt

Chancellor’s Honors Program Projects

No abstract provided.

Role Of Ubiquitin E3 Ligase Breast Cancer Associated Gene 2 (Bca2) In Sumoylation, Fareea Khaliq

Honors College Theses

As the occurrence of breast cancer increases around the world, the need for new therapeutic medicine becomes more vital to sustain the population. In order to accomplish this, specific mechanisms need to be understood to gain a perspective on the overall process of breast cancer development. One mechanism that is being researched is SUMOylation. The SUMOylation reaction uses small ubiquitin-like modifier (SUMO) proteins, which act as a type of post-translational modification that is necessary in order to preserve protein homeostasis and regulate cellular processes including apoptosis, cell proliferation, and response to stress. The SUMOs attach to a target protein through …

Identification Of Epithelial Stromal Interaction 1 And Epidermal Growth Factor Receptor As Novel Kruppel-Like Factor 8 Targets In Promoting Breast Cancer Progression, Tianshu Li

Electronic Theses and Dissertations

Breast cancer is the major cause of cancer death among women worldwide. Understanding the mechanisms underlying breast cancer progression remains urgent for developing effective treatment strategies to eliminate breast cancer mortality. Our recent studies have demonstrated that Krüppel-like transcriptional factor 8 (KLF8) plays a critical role for breast cancer progression. Other studies have shown that Epithelial stromal interaction 1 (EPSTI1), a recently identified stromal fibroblast-induced gene in non-invasive breast cancer cells and epidermal growth factor receptor (EGFR) are highly overexpressed in aggressively invasive breast carcinomas including triple negative breast cancers. In this thesis project, we demonstrate high co-overexpression of KLF8 …

Acidic Pericellular Ph: Effects On Proteolysis And Gene Expression As Determined In 3d Models Of Breast Carcinoma, Jennifer M. Rothberg

Wayne State University Dissertations

Among the non-cellular microenvironmental factors that contribute to malignancy of solid tumors is an acidic peritumoral pH. The first objective was to determine if an acidic extracellular pH observed in vivo (i.e., pHe 6.8) affects the activity of proteases, such as cathepsin B, that contribute to degradation of collagen IV by tumor cells when grown in biologically relevant three-dimensional cultures. At pHe 6.8 there were increases in pericellular active cysteine cathepsins and in degradation of DQ-collagen IV, which was partially blocked by a cathepsin B inhibitor. Imaging probes for active cysteine cathepsins localized to tumors in vivo. The amount of …