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

Tao Lu, Lyudmila G. Burdelya, Shannon M. Swiatkowski, Alexander D. Boiko, Philip H. Howe, George R. Stark, Andrei V. Gudkov

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7112-7117
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number18
DOIs
StatePublished - May 4 2004
Externally publishedYes

Keywords

  • ELISA
  • Prostate cancer
  • Smad
  • Small interfering RNA

ASJC Scopus subject areas

  • General

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