Date of Award
Open Access Master's Thesis
Master of Science in Biological Sciences (MS)
Administrative Home Department
Department of Biological Sciences
Committee Member 1
Committee Member 2
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 release from their respective complexes. Recently, CDK inhibitors have been proven to be effective chemotherapeutics, as they effectively lock pRb and p130 in their cell cycle repressive functions. Unfortunately, many ovarian tumors remain resistant to CDK inhibitor treatment. However, to date, no study has systematically evaluated how ovarian cancer affects both pRb and p130 function. Using flow cytometry, we confirmed that the SKOV3 ovarian cancer cell line responds to CDK inhibition but the OVCAR3 ovarian cancer cell line does not respond to CDK inhibition. Using western blot and expression analysis, we evaluated pRb and p130 response to CDK inhibition in SKOV3 cells, as compared to normal human foreskin fibroblasts (HFFs). We observed that although both pRb and p130 protein remain similarly expressed throughout the cell cycle, repression of 2 cell cycle genes, CCNB2 and MCM5, in CDK inhibited cells appears to be perturbed in the SKOV3 cell line, as compared to HFF cells. This study will lay the groundwork for future studies aimed to differentiate whether pRb or p130 dysfunction is causing the cell cycle gene misregulation we observed in the SKOV3 cell line.
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Rotman, Lydia, "CANCER AND QUIESCENCE: INVESTIGATING HOW THE DREAM COMPLEX AND RETINOBLASTOMA REGULATE THE CELL CYCLE", Open Access Master's Thesis, Michigan Technological University, 2022.