Overexpression of bax sensitizes human breast cancer MCF-7 cells to radiation-induced apoptosis

✍ Scribed by Chouhei Sakakura; Elizabeth A. Sweeney; Tsutomu Shirahama; Yasuyuki Igarashi; Sen-itiroh Hakomori; Hirohisa Nakatani; Hiroyuki Tsujimoto; Tsutomu Imanishi; Masaharu Ohgaki; Takakuki Ohyama; Junya Yamazaki; Akeo Hagiwara; Toshiharu Yamaguchi; Kiyoshi Sawai; Toshio Takahashi

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 553 KB
• Volume: 67
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19960703)67:1<101::aid-ijc17>3.0.co;2-h

✦ Synopsis

Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy and ionizing radiation (IR). bax, which forms a heterddimer with bcl-2 and accelerates apoptosir, is not, or only weakly. expremed 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 damonstrate its role of modulating radiation-induced apoptosis. 6ux overexpression in MCF-7 cells by stable transfedion 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 p2 I about 5to 10-fold and dormregulated bcl-2 and bcl-Xr by 80-90% at 6 hr in both parent and bax stably transfected MCF-7 cells to the same degree. FACS analysis and DNA electmphoresis revealed that this sensitization was due to apoptoris. We suggest that exogenous box expression might be one of the factwr determining cellular radiosensitivity in MCF-7 breast cancer cells and may have therapeutic applications for enhancing radiation rensitiiity in breast cancer cells.