Overexpression of bax sensitizes human breast cancer MCF-7 cells to radiation-induced apoptosis.
Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy and ionizing radiation (IR). bax, which forms a heterodimer with bcl-2 and accelerates apoptosis, is not, or only weakly, expressed in most human breast cancer cells, and weak bax expression is considered to be related to the resistance of breast cancer cells to apoptosis. bax expression vector was introduced to human breast cancer MCF-7 cells, which exhibit weak expression of bax, to demonstrate its role of modulating radiation-induced apoptosis. bax overexpression in MCF-7 cells by stable transfection does not affect viability by itself, but each stable transfectant was more sensitive to IR than the parental MCF-7 cells. The degree of enhancement in radiosensitivity was dependent on the expression level of bax. IR upregulated p53 and p21WAF1 about 5- to 10-fold and downregulated bcl-2 and bcl-XL by 80-90% at 6 hr in both parent and bax stably transfected MCF-7 cells to the same degree. FACS analysis and DNA electrophoresis revealed that this sensitization was due to apoptosis. We suggest that exogenous bax expression might be one of the factors determining cellular radiosensitivity in MCF-7 breast cancer cells and may have therapeutic applications for enhancing radiation sensitivity in breast cancer cells.
Sakakura
C
C
The First Department of Surgery, Kyoto Perfectural University of Medicine, Kyoto, Japan.
Sweeney
E A
EA
Shirahama
T
T
Igarashi
Y
Y
Hakomori
S
S
Nakatani
H
H
Tsujimoto
H
H
Imanishi
T
T
Ohgaki
M
M
Ohyama
T
T
Yamazaki
J
J
Hagiwara
A
A
Yamaguchi
T
T
Sawai
K
K
Takahashi
T
T
D017209:Apoptosis / Q000528:radiation effects*; D001943:Breast Neoplasms / Q000473:pathology*; D004249:DNA Damage; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D011836:Radiation Tolerance; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein