Exploring a potential link between cell cycle regulation and Cancer Testis gene misregulation

Abstract

Oncogenesis and misexpression of germline genes like Cancer Testis (CT) genes, called the soma‐to‐germline transformation, are commonly linked, but the mechanisms that drive the phenomenon remain underexplored. In the model system Caenorhabditis elegans, a soma‐to‐germline transformation occurs when the function of the highly conserved DREAM complex (for Dp, Retinoblastoma(Rb)‐like, E2F, and MuvB) is attenuated. In mammalian cells, DREAM's activity overlaps with the Retinoblastoma(Rb) protein to mediate establishment of cell cycle exit into quiescence, or G0. We hypothesize that CT gene misexpression in cancer cells occurs following loss of DREAM and Rb activity, similar to the soma‐to‐germline transformations that occur in C. elegans. Therefore, we expect that cancer cell lines that express CT genes will be unable to maintain an effective cell cycle exit. To test our hypothesis, cell cycle distributions of 8 cancer cell lines were analyzed using propidium iodide (PI) staining and flow cytometry before and after serum starvation. We observed that only 3 of the cell lines failed to arrest under growth limiting conditions, with the other 5 exhibiting some enrichment in G0/G1, indicating that these cell lines that did not arrest might exhibit upregulated expression of CT genes, and DREAM complex and Rb are deregulated. However, the cell lines that we observe G0arrest may still be dysfunctional in either DREAM complex or Rb activity. Therefore, we will next test expression analysis will test whether CT genes are differentially regulated between these groups and whether DREAM and/or Rb regulation is attenuated. This study is the first step towards understanding whether cell cycle regulation and the soma‐to‐germline transformation are linked in mammalian cells.Support or Funding InformationThe Saudi Arabian Cultural Mission (SACM)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.