Molecular Biology Commons^™

Repositioning Propranolol To Block Mitogenic Signaling In Breast Cancer, Alexa Noel Montoya

Open Access Theses & Dissertations

Breast cancer is the second most diagnosed cancer among women and is about 30% of all new cases of female cancers each year. It is projected that 1 in 8 every U.S. woman (about 13%) develop invasive breast cancer over the course of her lifetime. While advances in cancer research have made it possible to elucidate several breast cancer genomic subtypes, and develop new novel therapies, many of these agents are associated with significant toxicity, as well as high costs. A retrospective cross-sectional study of 404 breast cancer patients was performed to determine the effect of β-blocker usage on tumor …

The Role Of Cpeb2 Alternative Splicing In Tnbc Metastasis, Shaun C. Stevens

USF Tampa Graduate Theses and Dissertations

Breast cancer is the second leading cause of cancer-related deaths for women in the U.S. Although the overall 5-year survival rate for breast cancer is 90%, this rate drops substantially for triple-negative breast cancer (TNBC) due to its high metastatic potential. Furthermore, there is a lack of targeted therapeutics for TNBC, and clinical trials have been largely unsuccessful. These characteristics validate the need for identifying novel therapeutic targets for the treatment of TNBC. The study of alternative splicing (AS) has emerged as a powerful tool to elucidate the molecular underpinnings driving cancer.

Our lab has identified cytoplasmic polyadenylation element-binding protein …

The Role Of Reactive Oxygen Species In Regulating Macrophage And Fibroblast Activation Within The Breast Cancer Tumor Microenvironment, Brandon J. Griess

Theses & Dissertations

The tumor microenvironment (TME) is a key determining factor in breast cancer, especially the more aggressive subtype triple negative breast cancer (TNBC). The activated fibroblasts and macrophages within the TME have many tumor promoting functions. Therefore, targeting their activation presents a novel therapeutic approach in TNBC. My work studied the role of reactive oxygen species (ROS) during fibroblast and macrophage activation in breast cancer.

My studies showed that expression of the secreted antioxidant enzyme, EcSOD, is silenced in breast cancer samples, in part, via increased promoter methylation. The re-expression of EcSOD inhibited c-Met activation in the TNBC cell line, MDA-MB231. …

Molecular And Biochemical Studies Of Several Novel Estrogen Receptor Alpha-Interacting Proteins In Breast Cancer Cells, Ahmed Edan Dhamad

Graduate Theses and Dissertations

Breast cancer is the second leading cause of cancer-related death in women, and approximately 70% of incidences are estrogen receptor (ER)-positive breast cancer. ERα and its interacting proteins play a key role in the development and progression of breast cancer. However, how ERα regulates its target gene expression and hence cell proliferation is not fully understood. To enhance our understanding of the molecular mechanism by which ERα regulates gene expression, we used a quantitative proteomic method to identify cellular proteins that interact with ERα. The first group of proteins that were identified to associate with ERα are heat shock proteins …

The Roles Of Malt1 In Nf-Κb Activation And Solid Tumor Progression, Deng Pan

Dissertations & Theses (Open Access)

The transcription factor NF-κB plays a central role in many aspects of biological processes and diseases, such as inflammation and cancer. Although it has been suggested thatNF-κB is critical in tumorigenesis and tumor progression, the molecular mechanism by which NF-κB is activated in solid tumor remains largely unknown. In the current work, we focus on growth factor receptor-induced NF-κB activation and tumor progression, including epidermal growth factor receptor (EGFR)-induced NF-κB in lung cancer and heregulin receptor (HER2)-induced NF-κB in breast cancer. We found that Mucosa-associated lymphoma translocation protein 1 (MALT1), also known as paracaspase, is required for EGFR-induced NF-κB activation …

Evaluation Of Wild Yam (Dioscorea Villosa) As A Demethylating Agent And Its Anti Metastatic Activity In Human Breast Cancer Cells, Pranapda Aumsuwan

Electronic Theses and Dissertations

No abstract provided.

Estrogen Receptor Beta Is A Negative Regulator Of Mammary Cell Proliferation, Xiaozheng Song

Graduate College Dissertations and Theses

The mammary gland cell growth and differentiation are under the control of both systemic hormones and locally produced growth factors. Among all these important hormones and growth factors, estrogen plays a central role in mammary gland development. The biological function of estrogen is mediated by estrogen receptor α (ERα) and estrogen receptor β (ERβ). Both ERα and ERβ are expressed in the mammary gland, but with distinct expression patterns. In the mammary gland, ERα has been proved to be the estrogen receptor that mediates the mitogenic function of estrogen. However the function of ERβ in mammary cell proliferation is less …

Prolactin And Isplatin Combination Treatment Inhibit Tumorspheres Formation And Tumor Growth In Mice, Eric Hingleung Lee

All Dissertations

Cancer stem cells (CSCs) are defined as a small population of tumor initiating cells that are responsible for the initiation, development, progression, and recurrence of cancer. The chemo and radiation resistance of CSCs remains one of the major obstacles in conventional anti-cancer therapies. One of the reasons that conventional chemotherapeutics are not effective in targeting CSCs is that CSCs are usually in a non-proliferative or dormant state. In this perspective, targeting CSCs by inducing its proliferation and differentiation and simultaneously applying chemotherapeutics may be an alternative approach. The current study investigates the effect of prolactin (PRL), a hormone intimately involved …

Novel Role Of Erbb-2 In Inhibition Of Jagged-1-Mediated Trans-Activation Of Notch In Breast Cancer, Kinnari Pandya

Dissertations

The ErbB-2 gene is amplified and the resulting protein product overexpressed in 15-30% of breast tumors, and associated with aggressive behavior and poor overall survival. Currently, there are two FDA approved therapies targeting ErbB-2 for the treatment of ErbB-2 positive breast cancer: trastuzumab, a humanized monoclonal antibody is directed against the extracellular domain of ErbB-2 and lapatinib, a dual EGFR/ErbB-2 tyrosine kinase inhibitor. Unfortunately, anti-ErbB-2 therapy resistance remains a major problem in metastatic breast cancer. Our data suggested that gene amplification or overexpression of ErbB-2 inhibits Notch-1 transcriptional activity and trastuzumab or lapatinib increased

Notch-1 transcriptional activity. Furthermore, Notch-1 is …

Stromal-Epithelial Interactions Modulate Cross Talk Between Prolactin Receptor And Her2/Neu In Breast Cancer, Cong Xu

All Dissertations

The tumor microenvironment is a crucial factor in breast tumorigenesis. Tumor epithelial cells maintain 3D structure in tumor stroma and they interact with soluble factors secreted by stromal cells such as cancer associated fibroblasts (CAFs) or directly with the extracellular matrix (ECM). Recent studies have shown that the hormone prolactin (PRL) promotes the proliferation and survival of breast cancer cells in part via the transactivation of human epidermal growth factor receptor 2 (HER2), also known as Neu in rodents. A PRL receptor (PRLR) antagonist, G129R, has been demonstrated not only to be able to directly inhibit PRLR activation but also …

Suppression Of Chronically Induced Breast Carcinogenesis And Role Of Mesenchymal Stem-Like Cells, Kusum Rathore

Doctoral Dissertations

Sporadic breast cancers are mainly attributable to long-term exposure to environmental factors, via a multi-year, multi-step, and multi-path process of tumorigenesis involving cumulative genetic and epigenetic alterations in the chronic carcinogenesis of breast cells from a non-cancerous stage to precancerous and cancerous stages. Epidemiologic and experimental studies have suggested that various dietary compounds like green tea and grape seed may be used as preventive agents for breast cancer control. In this research, I have developed a cellular model that mimics breast cell carcinogenesis chronically induced by cumulative exposures to low doses of environmental carcinogens. I used the chronic carcinogenesis model …

A Novel Function For Aurora B Kinase In The Regulation Of P53 By Phosphorylation, Chris P. Gully

Dissertations & Theses (Open Access)

The mitotic kinase Aurora B plays a pivotal role in mitosis and cytokinesis and governs the spindle assembly checkpoint which ensures correct chromosome segregation and normal progression through mitosis. Aurora B is overexpressed in breast and other cancers and may be an important molecular target for chemotherapy. Tumor suppressor p53 is the guardian of the genome and an important negative regulator of the cell cycle. Previously, it was unknown whether Aurora B and p53 had mutual regulation during the cell cycle. A small molecule specific inhibitor of Aurora B, AZD1152, gave us an indication that Aurora B negatively impacted p53 …

The Role Of Brca1 Domains And Motifs In Tumor Suppression, Aneliya Velkova

USF Tampa Graduate Theses and Dissertations

Individuals that carry deleterious mutations in the breast and ovarian cancer susceptibility gene 1 (BRCA1) have much more elevated risk to develop breast and/or ovarian cancer than the individuals from the general population. The BRCA1 gene product has been implicated in several aspects of the DNA damage response, but its biochemical function in these processes has remained elusive. In order to probe BRCA1 functions we conducted a yeast two-hybrid screening to identify interacting partners to a conserved motif (Motif 6) in the central region of BRCA1. In this dissertation, we report the identification of the actin-binding protein Filamin A (FLNA) …

Notch Regulation Of Human Breat Cancer Progression: Contrasting Roles For Notch Signaling, Christine F. O'Neill

Electronic Theses and Dissertations

Notch signaling is associated with activation of either oncogenic or tumor suppressor activities. The human mammary adenocarcinoma cell line, MDA-MB-231, was characterized in vitro and in xenografts in vivo to test the hypothesis that activation of Notch signaling regulates mammary tumor phenotype. Notch 1, Notch2, and Notch4 signaling was compared by stable expression of their constitutively active intracellular domains (ICD). Notch4 activation led to enhanced tumorigenicity, in addition to increased cell proliferation and survival in vitro, whereas the activation of Notch 1 or Notch2 decreased cell proliferation and survival, in which Notch2 increased apoptosis. Stably transfected cell lines were …