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Possible Involvement of bcl-2 Suppression in Wild-Type p53 Gene-Dependent Cell Growth Repression in Rat Osteosarcoma Cells
Kanya Honoki
Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan
Toshifumi Tsujiuchi
Department of Oncological Pathology, Nara Medical University, Kashihara, Nara, Japan
Masahiro Tsutsumi
Department of Oncological Pathology, Nara Medical University, Kashihara, Nara, Japan
Akira Kido
Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan
Toru Morishita
Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan
Masatoshi Yoshimoto
Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan
Yoshizumi Miyauchi
Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan
Yoshio Mii
Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan
Susumu Tamai
Department of Orthopedic Surgery, Nara Medical University, Kashihara, Nara, Japan
Yoichi Konishi
Department of Oncological Pathology, Nara Medical University, Kashihara, Nara, Japan
We recently obtained 3 cloned cell lines demonstrating the p53 mutation from a lung metastatic nodule of a rat transplantable osteosarcoma. In this study, we applied wild-type p53 gene transfer to the rat osteosarcoma cells by lipofection to investigate the effects on cell growth, expression of genes such as waf1/p21, bcl-2, and bax, and nucleosomal DNA fragmentation due to apoptosis. Reconstitution of the p53 gene inhibits cellular growth, and this growth-suppressive effect is partly due to apoptosis involving bcl-2 gene suppression in this tumor type. This rat osteosarcoma model is similar in biologic behavior to human cases and thus is very suitable for further investigation of tumorigenesis and gene therapy for osteosarcoma.
Key Words: Osteosarcoma rat p53 waf1/p21 bcl-2 bax apoptosis
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Toxicologic Pathology, Vol. 28, No. 4,
575-579 (2000)
DOI: 10.1177/019262330002800411

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