TGF- β1-mediated apoptosis associated with SMAD-dependent mitochondrial Bcl-2 expression

Clin Lymphoma Myeloma Leuk. 2012 Apr;12(2):138-43. doi: 10.1016/j.clml.2011.12.001. Epub 2012 Jan 31.

Abstract

Background: Transforming growth factor (TGF) β1 can elicit various cellular responses, including inhibition of cell growth, migration, differentiation, and apoptosis. In addition, TGF-β1 is able to induce apoptosis in certain lymphomas.

Methods: In the present study, the role of SMADs, Bax, Bcl-xl, and Bcl2 was characterized in 2 B-lymphoma cell lines, Burkitt and pre-B cell.

Results: Apoptosis was detected after exposure of TGF-β on Raji and Nalm 6 cell lines and was evaluated by flow cytometry by using annexin V, reverse transcriptase-polymerase chain reaction, and Western blot analysis. Flow Cytometry With Cell Sorting analysis showed that apoptosis could be observed after 24 hours of TGF-β treatment and was continued after 48 hours. TGF-β downregulated the Bcl-xl and Bcl-2, whereas the Bax was upregulated. Furthermore, messenger RNA of SMAD6 and SMAD7 showed the significant upregulation.

Conclusion: The results indicated that alteration in gene expression and protein level may determine the induction of apoptosis pathway in these lymphoma cell lines exposed to TGF-β.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression / drug effects*
  • Humans
  • Lymphoma, B-Cell / metabolism
  • Mitochondria / genetics*
  • Mitochondria / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Smad Proteins / genetics
  • Smad Proteins / metabolism*
  • Smad6 Protein / genetics
  • Smad6 Protein / metabolism
  • Smad7 Protein / genetics
  • Smad7 Protein / metabolism
  • Transforming Growth Factor beta1 / pharmacology*
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • Smad Proteins
  • Smad6 Protein
  • Smad7 Protein
  • Transforming Growth Factor beta1
  • bcl-2-Associated X Protein
  • bcl-X Protein