Honors Capstone Project
Date of Submission
Dr. Thomas P. Fondy
Dr. Michael S. Cosgrove
Arts and Science
Capstone Prize Winner
Won Capstone Funding
Sciences and Engineering
Biochemistry | Biochemistry, Biophysics, and Structural Biology
mTOR is a kinase protein meaning it phosphorylates target proteins affecting their cell signaling properties1. The drug Rapamycin, analogs of Rapamycin, and cell signaling proteins that interact with mTOR control the activities mediated by mTOR1. mTOR is located in the cytoplasm at a convergent point of many signaling pathways that regulate a multiplicity of cellular processes including metabolism that precede cell enlargement (cell “growth”), cell proliferation (cell division), and angiogenesis1,2. Cells with mTOR inappropriately activated can proceed with cell enlargement and cell proliferation in the absence of normal cell signaling2. Rapamycin and Rapamycin analogs can inhibit mTOR and prevent cell enlargement that precedes cell proliferation3,4.
We wanted to know if there is a concentration of Rapamycin that will inhibit cell enlargement and proliferation of normal human hematopoietic stem cells (HSC) under conditions that will still permit enlargement and proliferation of human U937 leukemia cells. We performed experiments where we treated HSC and U937 cells with Rapamycin. We compared the results of these experiments to see whether there is a dose response difference to Rapamycin between the two cell types.
We found that cell size of both HSC and U937 leukemia cells was affected to comparable levels by Rapamycin at low nanomolar concentrations. However, Rapamycin appeared to have a startling differential effect on cell proliferation of HSC as compared to U937 cells. HSC proliferated very slowly or not at all in the presence of low nM concentrations of Rapamycin. U937 cells on the other hand were able to proliferate more strongly even at very high concentrations of Rapamycin. Rapamycin inhibited the rate of cell proliferation to some extent but it did not prevent the U937 cells from completing cell division and increasing in number.
Krawiec, Gabriela, "mTOR in Cell Signaling and Size Enlargement as a Target for the Chemico-Physical Therapy of Cancer" (2010). Honors Capstone Projects - All. 354.
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