Bio. Sci. Master's Defense: Sabha Alhewati
Advisor: Paul Goetsch
Presentation Title: Misexpression of Cancer/testis (CT) genes in tumor cells and the role of DREAM complex and the retinoblastoma protein (Rb) in soma-to-germline transformation
Abstract: Misexpression of germline genes like Cancer Testis (CT) genes, called a soma-to-germline transformation, is a phenomenon linked to tumorigenesis. However, the mechanisms underlying this phenomenon are poorly understood. A soma-to-germline transformation in Caenorhabditis elegans occurs due to the loss function of the highly conserved DREAM (Dp, Retinoblastoma (Rb)-like, E2F, and MuvB) transcriptional repressor complex, which is related to the Retinoblastoma protein (pRb) tumor suppressor. In mammalian cells, the overlapping activities of the DREAM complex pRb are essential for cell cycle exit. We hypothesize that the expression of CT genes in malignant cells occurs because of the loss of activities of DREAM complex or pRb, similar to how the soma-to-germline transformation occurs in C. elegans. Thus, we expect cancer cells that express CT genes will either fail to arrest in G0 or display defective repression of key cell cycle genes. We tested 10 human cancer cell lines for sensitivity to limiting growth conditions using flow cytometry. We found 3 cell lines did not arrest in G0/G1 in response to serum starvation, indicating that DREAM and pRb are inactive. However, we did not observe greater expression of CT genes in these 3 cell lines compared to the cell lines that respond normally to serum starvation. Therefore, we tested if either DREAM or pRb dysfunction is correlated with CT misexpression using expression analysis of cell cycle genes and reporter transfection assays. Cell cycle gene regulation was variably perturbed in all tested human cancer cell lines, making a link between DREAM or pRb and CT misregulation ambiguous. Together, these studies will facilitate future studies into the link between cell cycle regulation and CT upregulation in cancer cells.
Thursday, November 14, 2019 at 10:00 a.m. to 12:00 p.m.
Dow Environmental Sciences and Engineering Building, 743
1400 Townsend Drive, Houghton, MI 49931