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-kappaB, essential for survival and resistance to apoptosis in many tumors, is not well understood. We find that transforming growth factor beta2 (TGFbeta2), pre-dominantly in its latent form, is secreted by several different types of tumor cell lines that exhibit constitutively active NF-kappaB and that TGFbeta2 potently stimulates the activation of NF-kappaB in reporter cells. Suppression of TGFbeta2 expression by small interfering RNA kills prostate cancer Pc3 cells, indicating that the TGFbeta2-NF-kappaB path-way is important for their viability. These findings identify TGFbeta2 as a potential target for therapeutic strategies to inhibit the growth of tumor cells that depend on constitutively active NF-kappaB, or to sensitize them to treatment with cytotoxic drugs.