Induction of the WAF1/CIP1 protein and apoptosis in human T-cell leukemia virus type I-transformed lymphocytes after treatment with adriamycin by using a p53-independent pathway.
The WAF1/CIP1 protein has been identified as a downstream mediator of the tumor suppressor p53 in regulating cell cycle progression through a G1-phase check-point. Recent work has implicated the functional status of p53 as a critical determinant in the apoptotic response of certain cell lines to DNA damaging agents. By using human T-cell leukemia virus type I-transformed lymphoid cell lines that differ in their level and function of wild-type p53, we investigated the induction of WAF1/CIP1 and apoptosis after exposure to Adriamycin, a genotoxic agent. We found that regardless of the p53 status in these cell lines, WAF1/CIP1 RNA was rapidly induced in response to Adriamycin treatment. An elevated level of WAF1/CIP1 protein was observed as well. Additionally, we demonstrated that apoptosis was induced in all cell lines analyzed despite some having functionally inactive p53 protein. Our data suggest that a p53-independent pathway may play a role in the apoptotic response observed in some cell lines after exposure to DNA damaging agents.
Gartenhaus
R B
RB
Department of Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, NY 11040, USA.
Wang
P
P
Hoffmann
P
P
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D004249:DNA Damage; D017931:DNA Primers / Q000737:chemistry; D004317:Doxorubicin / Q000494:pharmacology*; D015368:Human T-lymphotropic virus 1; D006801:Humans; D008214:Lymphocytes / Q000382:microbiology* / Q000473:pathology; D008969:Molecular Sequence Data; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D000903:Antibiotics, Antineoplastic; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin