Bcl-2 blocks apoptotic signal of transforming growth factor-beta in human hepatoma cells.
Transforming growth factor-beta (TGF-beta) has been shown to induce apoptosis on normal hepatocytes and hepatoma cells both in vitro and in vivo. However, how the TGF-beta induces apoptosis is still not clear. We examined the expression of anti-apoptosis proteins and sensitivity to TGF-beta in three well differentiated human hepatoma cell lines. Two TGF-beta sensitive cell lines Hep3B and HuH7 totally lacked Bcl-2. In contrast, the TGF-beta resistant HepG2 cells expressed a substantial amount of Bcl-2. All three cell lines expressed equal amounts of Bcl-X(L), Bcl-X(S) and Bax. Overexpression of Bcl-2 in Hep3B and HuH7 cells protected them from TGF-beta-induced apoptosis. TGF-beta treatment increased intracellular peroxide production and suppressed the expression of glutathione-S-transferase in the Hep3B cells, and these effects were partially suppressed by the overexpression of Bcl-2. These results suggest that Bcl-2 may protect cell from TGF-beta-F-induced apoptosis by interfering TGF-beta generated signals leading to induce reactive oxygen species production.
Huang
Y L
YL
Institute of Biochemistry, National Yang-Ming University, Taipei, Taiwan.
Chou
C K
CK
D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D005982:Glutathione Transferase