Analysis of Fas and Fas ligand expression and function in lung cancer cell lines.
The aim of this study was to investigate the expression of Fas and Fas ligand (FasL) and to determine the significance of these molecules in lung cancer cell lines. Immunoblotting, RT-PCR and flow cytometric analyses were carried out to measure the expression of Fas and FasL and to examine their interactions and effects on cell growth and apoptosis. Fas and FasL were co-expressed in most of the cell lines but to varying degrees. Apoptosis induced by the agonistic anti-Fas antibody was significantly correlated with Fas expression (P=0.0075), whereas cisplatin-induced apoptosis was not. Upregulation of Fas and FasL expression by the administration of cisplatin was found in 7 of 11 (64%) and 9 of 11 (82%) cell lines, respectively. However, cisplatin-induced apoptosis was not suppressed by antagonistic anti-FasL antibody. Thus, our data indicated that Fas and FasL were co-expressed in lung cancer cell lines, and that Fas ligation induced by agonistic anti-Fas antibody is functional and induced apoptosis that was dependent on the levels of Fas expression. In contrast, Fas-FasL interactions appeared to be non-functional. Furthermore, our results suggest that cisplatin-induced apoptosis in lung cancer cells was independent of the Fas-FasL interaction.
Kawasaki
M
M
Research Institute for Diseases of the Chest, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, Japan. masayuki@kokyu.med.kyushu-u.ac.jp
Kuwano
K
K
Nakanishi
Y
Y
Hagimoto
N
N
Takayama
K
K
Pei
X H
XH
Maeyama
T
T
Yoshimi
M
M
Hara
N
N
D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002455:Cell Division; D002945:Cisplatin / Q000627:therapeutic use; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000378:metabolism
D000970:Antineoplastic Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D019014:fas Receptor; D002945:Cisplatin