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


CONCLUSIONS
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.
Cellular and Molecular Research Centre, Tehran University of Medical Sciences, Tehran, Iran. bakhflora@yahoo.com
Masoomeh
M
Bakhshayesh
Farhad
F
Zaker
Mehrdad
M
Hashemi
Majid
M
Katebi
Mansooreh
M
Solaimani
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D051905:Smad6 Protein / Q000235:genetics / Q000378:metabolism; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D051785:Smad Proteins; D051905:Smad6 Protein; D051906:Smad7 Protein; D053773:Transforming Growth Factor beta1; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein