Figure 4 .

Nf1 deletion in Chaos3 mammary tumors leads to increased activated RAS and sensitivity to PI3K and MAPK inhibitors. (A) Western blot analysis of Chaos3 tumors for NF1 and active RAS levels. The mammary tumors without detectable NF1 have homozygous deletions of Nf1 (Table S4), whereas the bone tumor and mammary tumor 22418 contain no Nf1 deletions. The presence of NF1 protein is inversely correlated with the level of activated (GTP-bound RAS). (B) NF1 and the Ras pathway. NF1 loss leads to increased cell proliferation and transcription of antiapoptosis genes because of failure to negatively regulate Ras. Inhibitors used in this study to slow proliferation of NF1-deficient tumor cells are shown in red type. Not all downstream targets are shown. RTK, receptor tyrosine kinase. (C) Cell proliferation assays showing sensitivity of Chaos3 tumors to rapamycin and Mek1 inhibitor PD98059. Line colors: red, HeLa; brown, MCF-7 and MDA-MB231; blue, PyVT; and black, Chaos3. BT, bone tumor; MT, mammary tumor; MTCL, mammary tumor cell line.