Figure 7

Phosphorylation at the T205 site inhibits FBW7 tumor suppressor function in pancreatic cancer. (A, B) Representative images of clone formation on plastic plates with SW1990 cell lines expressing FBW7 (wild type and T205A mutant) or empty vector. Quantification of cell growth is shown in B (n = 3, independent t-test, ^**P < 0.01). (C) Cell growth curve assay with SW1990 cell lines expressing FBW7 (wild type and T205A mutant) or empty vector (n = 3, independent t-test, ^**P < 0.01). (D, E) SW1990 cells stably expressing WT-FBW7, T205A-FBW7, or empty vector were injected into nude mice. At the indicated times, tumors were measured with Vernier calipers (mean ± SEM; n = 5, independent t-test, ^*P < 0.05). (F) Western blot analysis for c-Myc in SW1990 cell lines stably expressing Flag-WT-FBW7 or Flag-T205A-FBW7 (with empty vector as a negative control). (G) Representative images of tumor tissue from staining with antibodies against FBW7 and c-Myc. Scale bar, 100 μm. (H) Proposed model of how the Ras/Raf/MEK/ERK pathway regulates FBW7 stability to influence its tumor suppressive functions in pancreatic cancer.