Tumor suppressor function of STAT1 is cell-autonomous. (A) STAT1 was ectopically expressed in SSM1, SSM2, and SSM3 by retroviral transduction (STAT1) to levels comparable to the endogenous level in nontransduced (-) NMuMG. STAT1 was also overexpressed in NMuMG (STAT1). Retrovirus expressing GFP alone was used as a negative control (GFP). (B) STAT1 reconstitution in SSM2 and SSM3 resulted in 4.5- and 3.5-fold increases in early apoptosis (that is, annexin V-positive, 7-AAD-negative cells) 3 days post-transduction, respectively. **P < 0.005. (C) Tyrosine 701 is required for STAT1-mediated apoptosis in SSM2 and SSM3. Retrovirus expressing GFP, WT STAT1 (STAT1), and STAT1 mutants (Y701F or S727A) were transduced into SSM2 and SSM3. Mutation in Y701 (Y701F) abolished the ability of STAT1 to induce cell death, whereas that in S727 (S727A) was still capable of inducing cell death. SSM2, *P = 0.02. SSM3, *P = 0.04. P values were obtained with unpaired t test. ns, not significant; SSM, spontaneous STAT1-/- mammary (epithelial tumor cell line).