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The human lung adenocarcinoma cell line A549 is known to be resistant to tumor necrosis factor alpha (TNF-alpha)-mediated tumor cell lysis in spite of the expression of 55 kDa TNF receptor (TNF-R55) mRNA and its cell surface protein. In this study, we investigated the mechanism of TNF-alpha resistance and the role of two types of TNF receptors (TNF-R55 and TNF-R75 (75 kDa TNF receptor)). TNF-R55 or TNF-R75 cDNA was transfected into A549 cells. In addition, a C-terminal deletion mutant of TNF-R75 which lacks the intracellular domain of TNF-R75 was also transfected into A549 cells. We assessed the TNF-alpha-mediated tumor cell lysis of these transfected clones, and found that the cytotoxic effect increased in transfected clones highly expressing TNF- R55, but not in low-expression clones. As for TNF-R75, the cytotoxic effect of TNF-alpha was observed in TNF-R75-transfected clones even when expression was low. Furthermore, the cytotoxic effect was also observed in clones transfected with the deletion mutant of TNF-R75, as well as the complete TNF-R75. These results indicate that a certain level of expression of TNF-R75 is necessary for obtaining TNF-alpha-mediated tumor cell lysis in the absence of TNF-R75. On the other hand, the expression of TNF-R75 strongly induces TNF-alpha-mediated cytotoxicity through TNF-R55 in the absence of an intracellular signal via TNF-R75.
H Ohara, and
Y Hasegawa, and
T Kawabe, and
S Ichiyama, and
T Hara, and
Y Shimono, and
H Saito, and
K Shimokata
August 1988,
Cancer letters,
H Ohara, and
Y Hasegawa, and
T Kawabe, and
S Ichiyama, and
T Hara, and
Y Shimono, and
H Saito, and
K Shimokata
September 1989,
The Journal of urology,
H Ohara, and
Y Hasegawa, and
T Kawabe, and
S Ichiyama, and
T Hara, and
Y Shimono, and
H Saito, and
K Shimokata
July 1988,
The Journal of biological chemistry,
H Ohara, and
Y Hasegawa, and
T Kawabe, and
S Ichiyama, and
T Hara, and
Y Shimono, and
H Saito, and
K Shimokata
March 1995,
Journal of molecular medicine (Berlin, Germany),
H Ohara, and
Y Hasegawa, and
T Kawabe, and
S Ichiyama, and
T Hara, and
Y Shimono, and
H Saito, and
K Shimokata
March 1999,
Zhongguo fei ai za zhi = Chinese journal of lung cancer,
H Ohara, and
Y Hasegawa, and
T Kawabe, and
S Ichiyama, and
T Hara, and
Y Shimono, and
H Saito, and
K Shimokata
October 1988,
Nihon Hinyokika Gakkai zasshi. The japanese journal of urology,
H Ohara, and
Y Hasegawa, and
T Kawabe, and
S Ichiyama, and
T Hara, and
Y Shimono, and
H Saito, and
K Shimokata
May 1991,
The Journal of experimental medicine,
H Ohara, and
Y Hasegawa, and
T Kawabe, and
S Ichiyama, and
T Hara, and
Y Shimono, and
H Saito, and
K Shimokata
June 1990,
The Journal of biological chemistry,
H Ohara, and
Y Hasegawa, and
T Kawabe, and
S Ichiyama, and
T Hara, and
Y Shimono, and
H Saito, and
K Shimokata
January 1993,
Anticancer research,
H Ohara, and
Y Hasegawa, and
T Kawabe, and
S Ichiyama, and
T Hara, and
Y Shimono, and
H Saito, and
K Shimokata
January 2004,
Cancer research,
