Regulation of the Tumor Suppressor ARF by TGFβ in Human Cancer Cells

Since its discovery, p14ARF (p19Arf in mice) has been shown to be an important regulator of the cell cycle, carrying out this function through p53-dependent and independent mechanisms. ARF expression has recently been shown by the Skapek lab to be induced by TGFβ in mouse embryonic fibroblast and HeLa cells. TGFβ itself has been well characterized for its role as a "dual-edged sword," acting as a tumor suppressor or oncogene depending on the context. Though preliminary work has looked at the basic connections between TGFβ pathway components and their necessity for induction of ARF, many open questions remain, especially in translating findings from mouse to human cells. For my dissertation research, I have chosen to further investigate the regulation of TGFβ-driven induction of ARF. The knowledge gained through understanding TGFβ-dependent regulation of ARF is important in understanding disease progression and could also provide new avenues for cancer treatment through restoration of the TGFβ pathway to harness the tumor suppressive effects of p14ARF.