Secreted transforming growth factor β2 activates NF-κB, blocks apoptosis, and is essential for the survival of some tumor cells

The basis of constitutive activation of NF-κB, essential for survival and resistance to apoptosis in many tumors, is not well understood. We find that transforming growth factor β2 (TGFβ2), predominantly in its latent form, is secreted by several different types of tumor cell lines that exhibit constitutively active NF-κB and that TGFβ2 potently stimulates the activation of NF-κB in reporter cells. Suppression of TGFβ2 expression by small interfering RNA kills prostate cancer PC3 cells, indicating that the TGFβ2-NF-κB pathway is important for their viability. These findings identify TGFβ2 as a potential target for therapeutic strategies to inhibit the growth of tumor cells that depend on constitutively active NF-κB, or to sensitize them to treatment with cytotoxic drugs.