Secreted transforming growth factor [beta]2 activates NF-[kappa]B, blocks apoptosis, and is essential for the survival of some tumor cells

The basis of constitutive activation of NF-[kappa]B, essential for survival and resistance to apoptosis in many tumors, is not well understood. We find that transforming growth factor [beta]2 (TGF [beta]2), predominantly in its latent form, is secreted by several different types of tumor cell lines that exhibit constitutively active NF-KB and that TGF [beta]2 potently stimulates the activation of NF-[kappa]B in reporter cells. Suppression of TGF [beta]2 expression by small interfering RNA kills prostate cancer PC3 cells, indicating that the TGF [beta]2-NF-[kappa]B pathway is important for their viability. These findings identify TGF[beta]2 as a potential target for therapeutic strategies to inhibit the growth of tumor cells that depend on constitutively active NF-[kappa]B, or to sensitize them to treatment with cytotoxic drugs. prostate cancer | small interfering RNA | ELISA | Smad