Biochemistry, Biophysics, and Structural Biology Commons^™

The Evolution Of Tumor Suppressing Genes In Multicellular Organisms: Nature’S Prevention Of Oncogenesis, Melanie Perez

FIU Undergraduate Research Journal

The p53 gene family, a well-known group of genes, is the primary propagator of tumor-suppressing mechanisms in multicellular organisms. Although they are currently critical drug targets in cancer, the p53 family also serves specific functions in the development of multicellular organisms. In this paper, the current function, origin, and evolutionary purpose of the p53 family are reviewed in the evolution of multicellular organisms. The TP53 gene induces cellular responses such as apoptosis as a way to combat detrimental environmental and cellular factors that can damage the integrity of a cell’s DNA. The other two members of the p53 family are …

The Role Of Inositol Polyphosphate-4-Phosphatase Type Ii B (Inpp4b) In Obese Models And Endocrine Cancers, Manqi Zhang

FIU Electronic Theses and Dissertations

INPP4B is a dual-specificity phosphatase and a tumor suppressor in prostate and breast cancers. Progression of the prostate and breast cancers depends on the androgen receptor (AR) or estrogen receptor alpha (ERα) signaling, respectively. In this work we demonstrated that INPP4B reprograms ERα transcriptional activity in breast cancer. INPP4B maintains expression and protein levels of progesterone receptor (PR), an ERα direct target gene required for mammary gland development. Consistently we demonstrated that Inpp4b knockout severely impairs lateral branching in the mammary gland of maturing virgin females. In advanced prostate cancer, activation and transcriptional reprogramming of AR frequently coincides with the …

Impact Of San-Mediated Signaling On Glioblastoma And Neuroblastoma Metabolism, Monica Rodriguez Silva

FIU Electronic Theses and Dissertations

Glioblastoma (GBM) is the most common and aggressive type of brain cancer, with an average life expectancy of 15 months. The standard of care for GBM, surgery accompanied by radiation and chemotherapy (temozolomide-TMZ), has not changed in over 10 years illustrating the need for new and efficacious treatments. Therefore, it is imperative to improve our knowledge of GBM physiology to understand the mechanisms driving recurrence and chemoresistance so that more effective therapeutic options can be developed. Mitochondria-cell communication is key to monitor and maintain both mitochondrial and cellular health, and signaling events on the outer mitochondrial membrane (OMM) have emerged …

The Effect Of Target-Specific Biomolecules In Breast Cancer, Mohannad Garoub

FIU Electronic Theses and Dissertations

Cancer is the second leading cause of mortality in the United States and the World, therefore, early effective prevention, diagnosis, and therapy is needed. Estrogens play a major role in the initiation and progression of breast cancer. Elevated lifetime exposure to estrogens is associated with an increased risk of developing breast cancer. Estrogens through influencing mitochondria contribute to estrogen induced breast carcinogenesis; however, the exact mitochondrial mechanisms underlying the estrogen carcinogenic effect in breast tissue are not clearly understood. For this dissertation, the mitotoxic and cytotoxic effects of triphenylphosphonium cation (TPP) and Origanum majorana organic extract (OME) as well as …

Understanding Ten-Eleven Translocation-2 In Hematological And Nervous Systems, Feng Pan

FIU Electronic Theses and Dissertations

I proposed the study of two distinct aspects of Ten-Eleven Translocation 2 (TET2) protein for understanding specific functions in different body systems.

In Part I, I characterized the molecular mechanisms of Tet2 in the hematological system. As the second member of Ten-Eleven Translocation protein family, TET2 is frequently mutated in leukemic patients. Previous studies have shown that the TET2 mutations frequently occur in 20% myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN), 10% T-cell lymphoma leukemia and 2% B-cell lymphoma leukemia. Genetic mouse models also display distinct phenotypes of various types of hematological malignancies. I performed 5-hydroxymethylcytosine (5hmC) chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA …