Reduced expression of Bax in ceramide-resistant HL-60 subline.
Ceramide, the backbone of sphingolipids, has been reported to be involved in various cellular responses including apoptosis. We recently established and characterized a C2-ceramide-resistant HL-60 subline designated HL-CR. HL-CR cells were resistant to not only ceramide but also anti-cancer drugs including daunorubicin, etoposide, and cytosine arabinoside. To elucidate the mechanisms by which HL-CR cells became resistant to various apoptosis-inducing stimuli, the levels of Bcl-2 family proteins, which play crucial roles in drug-induced apoptosis, were compared between HL-CR and parental HL-60 cells. Among Bcl-2 family members, Bax, a pro-apoptotic Bcl-2 family protein, was highly expressed in HL-60 but was hardly detected in HL-CR cells. Transient transfection of bax-expressing plasmid, but not the vector alone, induced apoptosis in HL-CR cells. These results suggest that reduced expression of Bax might play a role in resistance to various apoptosis-inducing stimuli in HL-CR cells.
Sawai
Hirofumi
H
Department of Internal Medicine, Osaka Dental University, 8-1 Kuzuhahanazonocho, Hirakata, Osaka 573-1121, Japan. sawai@cc.osaka-dent.ac.jp
Kawai
Shinjiro
S
Domae
Naochika
N
D017209:Apoptosis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002518:Ceramides / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005822:Genetic Vectors; D018922:HL-60 Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D010957:Plasmids / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D014162:Transfection; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D002518:Ceramides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein