Molecular Biology Commons^™

Identification Of Novel Stat3 Target Genes Associated With Oncogenesis, Rachel Haviland

USF Tampa Graduate Theses and Dissertations

Cytokine and growth factor signaling pathways involving STAT3 are frequently constitutively activated in many human primary tumors, and are known for the transcriptional role they play in controlling cell growth and cell cycle progression. However, the extent of STAT3's reach on transcriptional control of the genome as a whole remains an important question. We predicted that this persistent STAT3 signaling affects a wide variety of cellular functions, many of which still remain to be characterized.

We took a broad approach to identify novel STAT3 regulated genes by examining changes in the genome-wide gene expression profile by microarray, using cells expressing …

Changes In Expression Of Akt Pathway Proteins Following Treatment With Rg3 In Vitro, Kathryn Schalkoff

All Theses

To assess changes in AKT pathway signaling, a recombinant protein of the G3 domain of rat laminin-5 (rG3) that specifically binds the alpha subunit of integrins α6β1 and α6β4 expressed on cancer cells (e.g., MDA-MB-231) was produced. This recombinant protein is believed to interrupt the intracellular signaling events of the AKT pathway, causing a decrease in proliferation and survival of cells after treatment. Viability assays confirmed an apoptotic effect of rG3 on cells in a dose-dependent manner. However, data from gene expression studies of Caspase-9, GRB10, and CDKNIB proved non-conclusive that rG3 is acting upon gene expression, leading to the …

Developmental Deregulation And Tumorigenesis Inhibition In 14-3-3zeta Knockout Mouse, Jun Yang

Dissertations & Theses (Open Access)

Cancer is second leading cause of death in the United States. Improving cancer care through patient care, research, education and prevention not only saves lives, but reduces health care cost as well. Breast cancer is the most leading cause of cancer incidence and cancer related death in women of the United States. 14-3-3s are a family of conserved proteins ubiquitously expressed in all eukaryotic organisms. They form complexes with hundreds of proteins by binding to specific phospho-serine/threonine containing motifs. In this way they regulate a variety of cellular processes and are involved in many human diseases especially cancer to our …

The Specific Role Of The Mll Cxxc Domain In Mll Fusion Protein Function, Laurie Ellen Risner

Dissertations

The MLL gene was first identified because it is involved in chromosome translocations which produce novel fusion proteins that cause leukemia. The CXXC domain of MLL is a cysteine rich DNA binding domain with specificity for binding unmethylated CpG-containing DNA. The CXXC domain is retained in oncogenic MLL fusions, and is absolutely required for the fusions to cause leukemia. This project explored the role of the CXXC domain by introducing structure-informed point mutations within the MLL CXXC domain that disrupt DNA binding, and by performing domain swap experiments in which different CXXC domains from other proteins, including DNMT1, CGBP and …

Notch-1 Specifically Activates Erk1/2 In Multiple Breast Cancer Subtypes, Allison Schuyler Rogowski

Master's Theses

Notch-1 is a cell fate regulatory protein and a potent breast oncogene. Notch-1 and its ligand Jagged-1 are over-expressed in human breast cancers that are associated with poor overall survival (Reedijk, Odorcic et al. 2005). Deregulated Notch signaling may contribute to tumorigenesis by increasing proliferation, inhibiting differentiation, and preventing apoptosis (Miele, Golde et al. 2006). The mitogen-activated protein kinase (MAPK) pathway is a critical cell signaling pathway that has been implicated in the development and progression of cancer (Hanahan and Weinberg 2000). Four major MAPK pathways are involved in both cell growth and apoptosis. The regulation of these pathways is …

Hedgehog Signaling: A Potential Therapeutic Target For Non-Small Cell Lung Cancer, Ma'in Yehya Maitah

Wayne State University Dissertations

The American Cancer Society estimated that 222,520 Americans were diagnosed with lung cancer and 157,300 died of lung cancer in 2010 (Jemal et al. 2009, 225-249;Jemal et al. 2011, 69-90). The clinical outcome of patients diagnosed with non-small cell lung cancer (NSCLC), the major lung cancer sub-types, is very poor, which calls for innovative research for finding novel therapeutic targets and agents for better treatment outcome.

Emerging evidences have suggested that a phenomenon called Epithelial-to-Mesenchymal Transition (EMT), which shares similar molecular characteristics with cancer stem-like cells, contributes to lung cancer treatment failure. In view of the fact that EMT process …