Molecular Biology Commons^™

Interferon Gamma Signaling In Ovarian Cancer Cells, Bijaya Gaire

Theses and Dissertations

Interferon gamma (IFNγ) is a pleiotropic cytokine that can have, depending on the cellular and molecular context, both anti-tumor and pro-tumorigenic functions. IFNγ expression can be induced in cancer cells in response to radiation therapy or immune checkpoint blockade used in cancer treatment. We have previously shown that IFNγ induces expression of the Bcl3 proto-oncogene in ovarian cancer (OC) cells, resulting in their increased proliferation and migration, but the mechanisms are unknown. Here, I demonstrate that the IFNγ-induced Bcl3 expression is dependent on JAK1 and STAT1 signaling, and on p65 NFkB. Furthermore, my data show that the IFNγ-induced Bcl3 expression …

Cancer And Quiescence: Investigating How The Dream Complex And Retinoblastoma Regulate The Cell Cycle, Lydia Rotman

Dissertations, Master's Theses and Master's Reports

An estimated 1.9 million people in the United States will be diagnosed with cancer in 2022. Cancer is characterized by uncontrolled cell growth, resulting from loss-of-function of key cell cycle regulatory proteins. The retinoblastoma protein (pRb) and p130, are two proteins that regulate cellular entry into the cell cycle. Both pRb and p130 repress expression of cell cycle genes, with pRb interacting with and suppressing E2F-DP transcriptional activators and p130 assembling in the DREAM transcriptional repressor complex. When normal cells receive signals to enter the cell cycle, cyclin and cyclin-dependent kinase (CDK) complexes phosphorylate pRb and p130, causing both to …

Toward A Topology-Based Therapeutic Design Of Membrane Proteins: Validation Of Napi2b Topology In Live Ovarian Cancer Cells, Leisan Bulatova, Daria Savenkova, Alsina Nurgalieva, Daria Reshetnikova, Arina Timonina, Vera Skripova, Mikhail Bogdanov, Ramziya Kiyamova

Journal Articles

NaPi2b is a sodium-dependent phosphate transporter that belongs to the SLC34 family of transporters which is mainly responsible for phosphate homeostasis in humans. Although NaPi2b is widely expressed in normal tissues, its overexpression has been demonstrated in ovarian, lung, and other cancers. A valuable set of antibodies, including L2 (20/3) and MX35, and its humanized versions react strongly with an antigen on the surface of ovarian and other carcinoma cells. Although the topology of NaPi2b was predicted

The Effect Of Cadmium On Ovarian Adenocarcinoma Cell Lines: An Investigation Of The Possible Mechanism Of Action, Haley Todd

Undergraduate Theses

Cadmium, a heavy metal and carcinogen, is an environmental and workplace contaminate. As a known endocrine disruptor, it can mimic the proliferative effects of estrogen and is classified as a metalloestrogen. While the proliferative effect of estrogen on cancerous cell growth has been well established, the effects of cadmium have not been fully examined. To determine if cadmium stimulates growth in two human ovarian adenocarcinoma cell lines, OVCAR3 and SKOV3, cells were treated for 48 hours with varying concentrations of cadmium, 0.001 µM – 10 µM, and growth was measured using a cell proliferation assay. Both cell lines showed a …

Prevalence Of Brca1 And Brca2 Mutations Among Breast And Ovarian Cancer Patients In Northern Emirates, Zahra Ahmed Mohammed Saeed

Theses

Breast Cancer (BC) is the most common cancer and the second most cause of death among women. Mutations in BRCA1 and BRCA2 genes confer high susceptibility to both breast and ovarian cancer. However, data on the prevalence of the BRCA1/2 mutations among breast and ovarian cancer patients is limited. The genetic component of breast cancer in the UAE is largely unknown and no study has evaluated the BRCA mutations status in breast and ovarian cancer patients in the UAE population. This retrospective study aimed to establish mutation frequencies of the BRCA genes in breast and ovarian cancer patients from the …

In Vitro Evaluation Of Ovarian Cancer Tumorigenesis As A Function Of Quinone Oxidoreducatse-1 And Cell Phenotype, Milcah S. Jackson

LSU Doctoral Dissertations

In vitro multicellular spheroids are attractive model systems for assessing genetic and epigenetic changes that occur in diseased tissues. Understanding how such alterations in gene and subsequent protein expression affect disease progression and metastasis, drug resistance, and recurrence is of great interest in cancer research. In this regard, examining expression and activity of proteins, such as those with cytoprotective ability that are overexpressed in cancer cells, in addition to cell phenotype (i.e., stem-like, epithelial, mesenchymal, or mixed), are two ways to evaluate genetic and epigenetic changes. Moreover, determining the impact that cytoprotective proteins and cell phenotype have on tumor formation …

Cellular Localization Of Rad51d Mutant Proteins And The Application Of Art To Increase Scientific Literacy In America, Claire L. Chabot

Senior Theses

Ovarian cancers are the leading cause of death from cancer of the female reproductive system. Approximately 50% of ovarian cancers have defects in the homologous recombination (HR) DNA repair pathway that is required for the repair of DNA double-stranded breaks. The status of HR genes, such as BRCA1, BRCA2, and the RAD51 family, contributes to ovarian cancer development as well as treatment decisions regarding chemotherapy, radiation, and immunotherapy. The overarching goal of this project is to identify new insights into HR that can integrate with Precision Medicine Initiatives and align with the goals of the Cancer Moonshot 2020 Program. I …

Myc Distant Enhancers Underlie Ovarian Cancer Susceptibility At The 8q24.21 Locus, Anxhela Gjyshi Gustafson

USF Tampa Graduate Theses and Dissertations

Ovarian cancer is a leading cause of death among women diagnosed with cancer. Mortality rate is high because an overwhelming majority of new cases are diagnosed with late-stage disease when the survival statistics are very poor with an overall 5-year survival rate of less than 40%. Despite the large burden of disease, the etiology of ovarian cancer is not well understood. In addition to linkage studies that have identified highly penetrant cancer susceptibility genes such as BRCA1 and BRCA2, the emergence of Genome Wide Association Studies (GWAS) in the last decade has facilitated the identification of common genetic variants with …

Targeting Ovarian Cancer And Endothelium With An Allosteric Ptp4a3 Phosphatase Inhibitor, Kelley E. Mcqueeney, Joseph M. Salamoun, James C. Burnett, Nektarios Barabutis, Paula Pekic, Sophie L. Lewandowski, Danielle C. Llaneza, Robert Cornelison, Yunpeng Bai, Zhong-Yin Zhang, John D. Catravas

Bioelectrics Publications

Overexpression of protein tyrosine phosphatase PTP4A oncoproteins is common in many human cancers and is associated with poor patient prognosis and survival. We observed elevated levels of PTP4A3 phosphatase in 79% of human ovarian tumor samples, with significant overexpression in tumor endothelium and pericytes. Furthermore, PTP4A phosphatases appear to regulate several key malignant processes, such as invasion, migration, and angiogenesis, suggesting a pivotal regulatory role in cancer and endothelial signaling pathways. While phosphatases are attractive therapeutic targets, they have been poorly investigated because of a lack of potent and selective chemical probes. In this study, we disclose that a potent, …

Inhibition Of Nuclear Factor-Kappa B Enhances The Tumor Growth Of Ovarian Cancer Cell Line Derived From A Low-Grade Papillary Serous Carcinoma In P53-Independent Pathway, Xue Xiao, Gong Yang, Peng Bai, Shunping Gui, Tri M. Bui Nguyen, +8 Additional Authors

Biochemistry and Molecular Medicine Faculty Publications

Background: NF-kB can function as an oncogene or tumor suppressor depending on cancer types. The role of NF-kB in low-grade serous ovarian cancer, however, has never been tested. We sought to elucidate the function of NF-kB in the low-grade serous ovarian cancer.

Methods: The ovarian cancer cell line, HOC-7, derived from a low-grade papillary serous carcinoma. Introduction of a dominant negative mutant, IkBαM, which resulted in decrease of NF-kB function in ovarian cancer cell lines. The transcription ability, tumorigenesis, cell proliferation and apoptosis were observed in derivative cell lines in comparison with parental cells.

Results: Western blot analysis indicated increased …

Circumventing Cisplatin Resistance In Ovarian Cancers Through Reactivation Of P53 By Non-Cross-Resistant Platinum Analogs, Michelle Martinez-Rivera

Dissertations & Theses (Open Access)

Abstract

CIRCUMVENTING CISPLATIN RESISTANCE IN OVARIAN CANCERS THROUGH REACTIVATION OF P53 BY NON-CROSS-RESISTANT PLATINUM ANALOGS

Michelle Martinez-Rivera, B.S.

Advisory Professor: Zahid H. Siddik, Ph.D.

Cisplatin (cis-Pt), an anticancer platinum (Pt) drug, is used widely in the treatment of several malignancies, such as ovarian cancer. This Pt compound induces DNA damage, which results in p53 activation through post-translational modifications, mainly phosphorylation, culminating in execution of programmed cell-death. However, despite initial therapeutic response to cis-Pt, clinical resistance to this drug emerges leading to disease progression. Pt-resistance phenotypes have been associated with dysfunction in the p53 signaling pathway. Therefore, an effort to understand …

The Cancer Genome Atlas (Tcga): Breast And Ovarian Cancers, Laura Ann Riccio

Senior Honors Projects

The field of genomics originated in the 1970’s starting with the sequencing of small organisms’ genomes such as the bacterium, Haemophilus influenzae, and the yeast, Saccharomyces cerevisiae. A genome is the complete ordered sequence of DNA bases (A, C, G, and T) comprising all of the protein- and RNA-coding genes, as well as all of the regulatory sequences necessary for the construction of an organism. Over time, scientists sequenced the genomes of larger and more complex organisms, eventually leading to the sequencing of the human genome. The Human Genome Project (HGP) was initiated in 1990 and took over ten …

The Therapeutic Targeting Of Folate Receptor Alpha Positive Tumors Via Folate Receptor Selective Novel 5- And 6- Substituted Pyrrolo [2,3-D]Pyrimidine Antifolates", Shermaine Kimberly Mitchell-Ryan

Wayne State University Dissertations

Ovarian Cancer is the fifth leading cause of cancer-related death of women in the United States. Epithelial Ovarian Cancer (EOC) constitutes 85-90% of malignancies within the ovary, with an alarming majority of these cases diagnosed at advanced stage. While most patients are initially highly responsive to the current treatment standard, there is a very high probability that they will recur with a drug resistant fatal disease. Currently there is no validated comprehensive model of disease progression for ovarian cancer, although tremendous progress has been made in understanding the origin of this disease and a putative precursor lesion has been identified …

The Interrelationship Of Brca1 185delag, Interleukin-1Β, And Ovarian Oncogenesis, Kamisha Woolery

USF Tampa Graduate Theses and Dissertations

While the etiology of ovarian cancer (OC) is not completely understood, evidence suggests that chronic inflammation may promote malignant transformation. However, familial history remains the strongest risk factor for developing OC and is associated with germline BRCA1 mutations, such as the 185delAG mutation. Normal human ovarian surface epithelial cells expressing the 185delAG mutant, BRAT, exhibit molecular and pathological changes that may contribute to OC oncogenesis. In the current study, I sought to determine whether BRAT could promote an inflammatory phenotype by investigating BRAT's impact on the expression of the proinflammatory cytokine, Interleukin-1β (IL-1β). Using a culture model system of normal …

Regulation Of The Tumor Suppresser P53 And Survivin By Ras And Ral Gtpases:Implications For Malignant Transformation, Awet G. Tecleab

USF Tampa Graduate Theses and Dissertations

Abstract

Although the critical role of the small GTPases Ras and Ral in oncogenesis has been well documented, much remains to be investigated about the molecular mechanism by which these GTPases regulate malignant transformation. The work under this thesis made two major contributions to this field. The first is the discovery that K-Ras, RalA and/or RalB are required for the maintenance of the high levels of the anti-apoptotic protein survivin in some human cancer cells, and the second is the demonstration that down regulation of K-Ras, RalA and/or RalB, but not Raf-1 or Akt1/2, stabilizes the tumor suppressor p53 and …

A Novel Link Between Akt1 And Twist1 In Ovarian Tumor Cell Motility And Invasiveness, Nirav Shah

Electronic Theses and Dissertations

Ovarian cancer results in more deaths per year than any other cancer of the female reproductive system. The low survival rate is partly due to the lack of early detection and the susceptibility to relapse. The AKT serine threonine kinase plays a pivotal role in hallmark cellular processes for the progression of ovarian cancer, including tumor cell growth and migration. Therapeutic targeting of pan-AKT has been problematic, in part due to feedback mechanisms and crosstalk with other pathways. The hypothesis for this study is that AKT 1, -2 and -3 isoforms may have different roles and regulate cell processes in …