The Role of the Cyclin-like Protein, Spy1, on Cell Cycle Progression and Liver Cancer
Standing
Undergraduate
Type of Proposal
Oral Presentation
Faculty
Faculty of Science
Faculty Sponsor
Dr. Lisa Porter
Proposal
Hepatocellular carcinoma (HCC) is the cause of approximately 1 million deaths per year, and accounts for 85-90% of all primary liver cancers. Its presence has been observed worldwide, survival rates are poor, and many risk factors put individuals at a higher chance of developing this disease. Effective therapies are limited leading to poor 5-year survival. The primary cell type of the liver, hepatocytes, display unique cell growth and proliferation properties. Hepatocytes become polyploid through development, which increases the DNA content in each cell, and they retain the potential to regenerate and proliferate. Increased polyploidy has been shown to be a protective factor in the development and progression of HCC. Misregulation of the cell cycle plays a critical role in the onset of HCC. Spy1 is an atypical cyclin-like protein that can induce progression through the cell cycle by binding to cyclin-dependent kinases (CDKs). This binding allowing for unique progression through various cell cycle checkpoints, and Spy1 is known to be elevated in HCC. A transgenic mouse model, MMTV-Spy1, that has decreased hepatocyte ploidy and increased susceptibility to liver tumour formation, will be utilized to study the effects of increased expression of Spy1 on hepatocyte regeneration, susceptibility to tumour formation and response to treatment. Expression of mediators of cell cycle progression, differentiation and metabolism in hepatocytes, such as p53, CCAAT/enhancer binding proteins (C/EBP), cyclin D and p27, will be examined. The results will provide insight into the effects that Spy1 has on cell cycle progression in hepatocytes, and may reveal a novel therapeutic target in the treatment of HCC.
Location
University of Windsor
Grand Challenges
Viable, Healthy and Safe Communities
The Role of the Cyclin-like Protein, Spy1, on Cell Cycle Progression and Liver Cancer
University of Windsor
Hepatocellular carcinoma (HCC) is the cause of approximately 1 million deaths per year, and accounts for 85-90% of all primary liver cancers. Its presence has been observed worldwide, survival rates are poor, and many risk factors put individuals at a higher chance of developing this disease. Effective therapies are limited leading to poor 5-year survival. The primary cell type of the liver, hepatocytes, display unique cell growth and proliferation properties. Hepatocytes become polyploid through development, which increases the DNA content in each cell, and they retain the potential to regenerate and proliferate. Increased polyploidy has been shown to be a protective factor in the development and progression of HCC. Misregulation of the cell cycle plays a critical role in the onset of HCC. Spy1 is an atypical cyclin-like protein that can induce progression through the cell cycle by binding to cyclin-dependent kinases (CDKs). This binding allowing for unique progression through various cell cycle checkpoints, and Spy1 is known to be elevated in HCC. A transgenic mouse model, MMTV-Spy1, that has decreased hepatocyte ploidy and increased susceptibility to liver tumour formation, will be utilized to study the effects of increased expression of Spy1 on hepatocyte regeneration, susceptibility to tumour formation and response to treatment. Expression of mediators of cell cycle progression, differentiation and metabolism in hepatocytes, such as p53, CCAAT/enhancer binding proteins (C/EBP), cyclin D and p27, will be examined. The results will provide insight into the effects that Spy1 has on cell cycle progression in hepatocytes, and may reveal a novel therapeutic target in the treatment of HCC.