| The Ly-6 family of glycosylphosphatidylinisotol proteins is excellent differentiation markers of immune cells during their development and they regulate signaling responses. Specifically, Ly-6A is up-regulated on several transformed cells, making it a potential biomarker for cancer detection and therapy. Previous work in our laboratory revealed that a transformed CD4+ T lymphocyte cell line shows growth inhibition and apoptotic cell death when Ly-6A protein is engaged. We investigated whether this mechanism involves p53, which is known to regulate the cell cycle and apoptotic cell death. The cell cycle is regulated by several proteins known as cyclin dependent kinases that bind cyclin proteins and usher the cell past checkpoints in the cell cycle. We find that while growth inhibition and cell death in the T cell line was p53 independent, the cell cycle inhibitor gene p27 becomes significantly up-regulated. In addition, we determined that the apoptotic pathway is intrinsic mitochondrial dependent. Furthermore, we extended this study beyond the analysis of one Ly-6A antibody and one T-cell line. We find that the responses were tied primarily to the extent of cross-linking with anti-Ly-6A antibody. Other transformed T-cell lines also exhibited growth inhibition and cellular death when the Ly-6A protein was engaged. |
