MNRR1 Inhibition, a Potential Therapeutic Avenue for Breast Cancer

Overview

Breast cancer affects hundreds of thousands of people each year. Cancer, defined as uncontrolled growth of cells, may occur due to changes in a cell which prevent normal cellular processes that regulate proliferation or cellular death (apoptosis). In breast cancer cells the protein Mitochondria Nuclear Retrograde Regulator 1 (MNRR1) is highly expressed compared to healthy cells. MNRR1, as the name suggests is a biorganellar protein that controls cellular function by acting in two compartments. In the mitochondria, it enhances energy production and inhibits apoptosis, whereas in the nucleus, it controls the transcription of genes involved in stress-responsive pathways. Since MNRR1 controls two key features of cancers- energy production which may 57 affect cellular growth; and apoptosis, we hypothesized that increases of MNRR1 seen in breast cancer lines may play a role in carcinogenesis. Previous work in our lab identified a compound that inhibits MNRR1. We tested if this compound by itself, or in combination with a bonafide anti-cancer drug (Daunorubicin) can prevent breast cancer cell growth and increase apoptosis. Our results indicate that MNRR1 inhibitor decreases cell number and increases cell death when used in combination with Daunorubicin. The current dose of Daunorubicin used in breast cancer treatment is highly toxic to healthy cells as well. These results suggest that MNRR1 is a potential drug target and its inhibition may improve the treatment paradigms by reducing the dose and therefore toxicity of drugs that are currently used in the treatment of breast cancer. MISSOURI Sleep It Off: Reversing Alzheimer’s Associated Cognitive Deficits Using Memantine Induced Sleep Oyinloluwa Ganiyu Timberland High School, Wentzville, MO Teacher Mrs. Theresa Cordonier, Timberland High School Previous studies recognized the role of GABA-A agonist 4,5,6,7-tetrahydro isoxazole-[5,4-c]pyridine-3-ol (THIP) in restoring both short-term and long-term cognitive function in a Drosophila model of Alzheimer’s disease (APP:BACE flies). Memantine is a mainstream Alzheimer’s disease medication that has been shown to slow disease progression, though without restoration of short-term cognitive function. As Drosophila represents an animal model that accurately reflects many aspects of Alzheimer’s disease, I hypothesized that memantine would not demonstrate the reversal of short-term cognitive deficits in transgenic APP:BACE flies to the extent to which THIP did in past studies. T o test this hypothesis, flies were separated into Vehicle and RU food which maintained them as controls or induced expression of APP:BACE and in turn, Alzheimer’s disease- like symptoms. After gene induction, flies were further split into treatment groups and short-term memory was tested in the Aversive Phototaxic Suppression assay, which trains flies to go against their innate phototaxic nature. The results which were limited by small sample sizes and high attrition rates showed no statistical significance of memantine treatment, therefore, failing to reject the null hypothesis.