TY - JOUR
T1 - Differential involvement of the CD95 (Fas/APO-1) receptor/ligand system on apoptosis induced by the wild-type p53 gene transfer in human cancer cells
AU - Fukazawa, Takuya
AU - Fujiwara, Toshiyoshi
AU - Morimoto, Yoshinori
AU - Shao, Jianghua
AU - Nishizaki, Masahiko
AU - Kadowaki, Yoshihiko
AU - Hizuta, Akio
AU - Owen-Schaub, Laurie B.
AU - Roth, Jack A.
AU - Tanaka, Noriaki
N1 - Funding Information:
This work was supported in part by grants from the Ministry of Education, Science, and Culture, Japan; by grants from the Ministry of Health and Welfare, Japan (Health Sciences Research Grants (Research on Human Genome and Gene Therapy)); by grants from the National Cancer Institutes and the National Institutes of Health (RO1CA45187) [JAR]; (Specialized Program of Research Excellence [SPORE] in Lung Cancer [P50-CA70907]); by gifts to the Devision of Surgery and Anesthesiology from Tenneco and Exxon for the Core Laboratory Facility; by the UTMD. Anderson Cancer Center Support Core Grant (CA16672); by a grant from the Mathers Foundation; and a sponsored research agreement with Introgen Therapeutics.
PY - 1999/4/1
Y1 - 1999/4/1
N2 - The CD95 (Fas/APO-1) system regulates a number of physiological and pathological processes of cell death. The ligand for CD95 induces apoptosis in sensitive target cells by interacting with a transmembrane cell surface CD95 receptor. We previously reported that the recombinant adenovirus-mediated transfer of the wild-type p53 gene caused apoptotic cell death in a variety of human cancer cells. To better understand the mechanism responsible for this cell death signaling, we have investigated the potential involvement of the CD95 receptor/ligand system in p53-mediated apoptosis. The transient expression of the wild-type p53 gene upregulated the CD95 ligand mRNA as well as protein expression in H1299 human lung cancer cells deficient for p53 and in DLD-1 and SW620 human colon cancer cells with mutated p53, all of which constitutively expressed CD95 receptor as shown by a flow cytometric analysis, and induced rapid apoptotic cell death as early as 24 h after gene transfer. However, the sensitivity to the cytolytic effect of agonistic anti-CD95 antibody (CH11) varied among these cell lines: CH11 induced apoptosis in H1299 cells, but not in DLD-1 and SW620 cells despite their abundant CD95 receptor expression, suggesting that the CD95 receptors on DLD-1 and SW620 cells might be inactivated. In addition, an antagonistic anti-CD95 ligand antibody (4H9) that interfered with the CD95-receptor-ligand interaction partially reduced the apoptosis induced by the wild-type p53 gene transfer in H1299 cells, whereas apoptosis of DLD-1 and SW620 cells occurred in the presence of 4H9. Taken together, these findings led us to conclude that the CD95 receptor/ligand system is differentially involved in p53-mediated apoptosis, suggesting that the restoration of the wild-type p53 function may mediate apoptosis through CD95 receptor/ligand interactions as well as an alternative pathway.
AB - The CD95 (Fas/APO-1) system regulates a number of physiological and pathological processes of cell death. The ligand for CD95 induces apoptosis in sensitive target cells by interacting with a transmembrane cell surface CD95 receptor. We previously reported that the recombinant adenovirus-mediated transfer of the wild-type p53 gene caused apoptotic cell death in a variety of human cancer cells. To better understand the mechanism responsible for this cell death signaling, we have investigated the potential involvement of the CD95 receptor/ligand system in p53-mediated apoptosis. The transient expression of the wild-type p53 gene upregulated the CD95 ligand mRNA as well as protein expression in H1299 human lung cancer cells deficient for p53 and in DLD-1 and SW620 human colon cancer cells with mutated p53, all of which constitutively expressed CD95 receptor as shown by a flow cytometric analysis, and induced rapid apoptotic cell death as early as 24 h after gene transfer. However, the sensitivity to the cytolytic effect of agonistic anti-CD95 antibody (CH11) varied among these cell lines: CH11 induced apoptosis in H1299 cells, but not in DLD-1 and SW620 cells despite their abundant CD95 receptor expression, suggesting that the CD95 receptors on DLD-1 and SW620 cells might be inactivated. In addition, an antagonistic anti-CD95 ligand antibody (4H9) that interfered with the CD95-receptor-ligand interaction partially reduced the apoptosis induced by the wild-type p53 gene transfer in H1299 cells, whereas apoptosis of DLD-1 and SW620 cells occurred in the presence of 4H9. Taken together, these findings led us to conclude that the CD95 receptor/ligand system is differentially involved in p53-mediated apoptosis, suggesting that the restoration of the wild-type p53 function may mediate apoptosis through CD95 receptor/ligand interactions as well as an alternative pathway.
KW - Adenovirus vector
KW - Apoptosis
KW - CD95
KW - CD95 ligand
KW - p53
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UR - http://www.scopus.com/inward/citedby.url?scp=0033119428&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1202561
DO - 10.1038/sj.onc.1202561
M3 - Article
C2 - 10327065
AN - SCOPUS:0033119428
SN - 0950-9232
VL - 18
SP - 2189
EP - 2199
JO - Oncogene
JF - Oncogene
IS - 13
ER -