Numb Modulation Regulates Ras+ Cancer Cells

Example 43

At 5 days post-transduction/post-plating, Ras+ cancer cells transduced with control HIV-EGFP lentivirus showed rapid proliferation and chaotic morphologies (FIG. 27A). The inset shows three round, brightly fluorescing cells whose appearance was consistent with cancer stem cells. In contrast, cells transduced with HIV-EGFP-Numb^{PRR−/PTB−} showed evidence of symmetrical, terminal divisions (cell pairs) on day 5, as well as reduced proliferation (FIG. 27B). In addition to blocking proliferation, transduction with HIV-EGFP-Numblike induced Ras+ cancer cells to adopt a phenotype consistent with normal breast epithelial cells (FIG. 27C). At 10 days post-plating/post-transduction, Ras+cancer cells transduced with control virus fluoresced more brightly than on day 5, but otherwise, continued to show the disorganization characteristic of breast cancer cells, in vitro (FIG. 27D). In contrast, on day 10, few, mostly small cells were present in with HIV-EGFP-Numb^{PRR−/PTB−} transduced culture (FIG. 27E). Meanwhile, additional cells reverting to a normal, breast epithelial phenotype were identifiable in HIV-EGFP-Numblike transduced cultures (FIG. 27F).