mTORC1 activation is transduced in CTCL cells preferentially by PI3K/Akt compared with MEK/ERK signaling pathway. CTCL cell lines (A) and CTCL and ALK + TCL (Sudhl-1) cell lines (B) were exposed for 1 hour to solvent, PI3K inhibitor wortmannin, MEK1/2 inhibitor U0126, or Syk inhibitor I at the indicated doses and analyzed in Western blots with the listed antibodies. The CTCL cell lines were also exposed to 2 nM wortmannin for 8 hours (readministered every 2 hours), 5 nM rapamycin, and evaluated for the proliferative (C) and apoptotic (D) cell rate. The effect on cell proliferation (E) and apoptosis (F) of combining rapamycin (0.5 nM) with wortmannin (10 nM) or U0126 (0.5 μM in panel E and 15 μM in panel F) was also determined in the 48-hour and 24-hour assays, respectively.