STAT1 provides tumor suppressor function in ALK+ ALCL. (A) Tet on-SupM2-STAT1C expressed an increased level of pSTAT1 and STAT1 in a doxycycline dose-dependent manner. STAT1 downstream targets IRF-7, T-bet, and SOCS-1 were all upregulated. In contrast, Survivin and BCL-2, two known STAT3 downstream targets, were downregulated in a dose-dependent manner. Cleaved caspase 3 and cleaved PARP were expressed, indicating the occurrence of apoptosis. (B) Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) studies that used Tet on-SupM2-STAT1C cells showed increased messenger RNA (mRNA) expression of IFN-γ and IRF-1 in a STAT1C dose-dependent manner. (C) When SupM2 and Karpas 299 cells were transiently transfected with STAT1C-flag for 24 hours, the increase of IFN-γ mRNA was also detected by using qRT-PCR. (D) By using Tet on-SupM2-STAT1C cells, we found a significant decrease in the number of viable cells with increasing doxycycline. (E) By using Tet on-SupM2-STAT1C cells, we found that STAT1C sensitizes cells to doxorubicin-induced apoptosis at 0.5 and 1.0 µM doxorubicin. (F) Colony formation significantly decreased with increasing doses of doxycycline and STAT1C expression. The right panel illustrates the morphology of the colonies (×40, ×100 magnification, respectively). (G-I) SCID mouse xenograft studies showed that the expression of STAT1C significantly decreased the tumorigenicity of Tet on-SupM2 STAT1C cells. Tet on-SupM2 EV cells were used as the negative controls. The xenografts and STAT1 expression levels in the harvested xenografts are also illustrated. Statistical significance was determined by using Student t test. *P < .05; **P < .01.