Wild type p53 reduces the size of tumors caused by bovine leukemia virus-infected cells.
Bat lung (BAT(2)CL6) cells infected with bovine leukemia virus (BLV) cause malignant tumors in nude mice that after 6 weeks subcutaneous growth, have an average volume of 0.3m(3). Uninfected bat lung cells (Tb 1 Lu) produce small benign neoplasms that average 0.003 cm(3). BAT(2)CL6 cells were transfected in vitro with expression vectors that produce wild type human or mutant p53. Production of human p53 in transfected BAT(2)CL6 cells was confirmed by immunoprecipitation of p53 and by immunohistochemical staining using anti-human p53 monoclonal antibodies. BAT(2)CL6 cells transfected with wild type p53 produced tumors in nude mice averaging 0.03 cm(3) whereas cells transfected with mutant p53 yielded tumors averaging 0.3cm(3). BAT(2)CL6 cell tumors after 1 week subcutaneous growth were transfected in situ with the wild type p53 gene. At 6 weeks tumor volume of in situ transfected tumors was similar to those resulting from cells transfected in vitro. Histopathologic examination and immunochemical staining of tumors produced in nude mice after wild type p53 treatment showed no significant differences when compared to tumors produced by untreated BAT(2)CL6 cells. Therefore, it is likely that the tumors produced by p53 treated-cells arose from cells that escaped transfection. The reduction of tumor size by restoration of wild type 53 may prove to be a useful therapy for BLV-induced tumors.
Dees
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Molecular Toxicology Group, Oak Ridge National Laboratory, Oak Ridge, TN 37831-6109, USA.
Godfrey
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VL
Schultz
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Travis
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D000818:Animals; D002417:Cattle; D002460:Cell Line; D002685:Chiroptera; D016583:Enzootic Bovine Leukosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D016158:Genes, p53 / Q000235:genetics / Q000502:physiology; D001909:Leukemia Virus, Bovine / Q000235:genetics; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009154:Mutation / Q000235:genetics; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
D016159:Tumor Suppressor Protein p53