Role of the p53 tumor suppressor gene in the tumorigenicity of Burkitt's lymphoma cells
- PMID: 9192833
Role of the p53 tumor suppressor gene in the tumorigenicity of Burkitt's lymphoma cells
Abstract
Burkitt's lymphoma (BL) cell lines carry a translocated c-myc gene and, in 60-80% of cases, exhibit mutations in the p53 tumor suppressor gene. We examined the potential role of the p53 gene in BL tumorigenicity using an in vitro assay that measures p53-dependent cell cycle arrest in the G1 phase of the cell cycle and an in vivo athymic murine model that detects differences in the tumorigenicity of BL cell lines. A highly significant inverse correlation was found between the ability of BL cells to arrest in G1 after irradiation and their tumorigenicity in athymic mice, consistent with the notion that loss of p53 function is associated with increased tumorigenicity. Inactivation of wild-type (wt) p53 function by expression of the human papillomavirus E6 protein in the AG876V BL cell line, which carries both wt and mutant p53 proteins, rendered the cell line significantly more tumorigenic in athymic mice. Transfection of the wt p53 gene into the p53 mutant and highly tumorigenic BL-41 cell line caused it to acquire wt p53 function and rendered it less tumorigenic in mice. In addition to confirming a role for the loss of p53 function in tumor progression, the data demonstrate that wt p53 protein can reduce BL tumorigenicity in vivo.
Similar articles
-
Role of the p53 tumor suppressor gene in cell cycle arrest and radiosensitivity of Burkitt's lymphoma cell lines.Cancer Res. 1993 Oct 15;53(20):4776-80. Cancer Res. 1993. PMID: 8402660
-
Wild-type p53 induces apoptosis in a Burkitt lymphoma (BL) line that carries mutant p53.Oncogene. 1993 Jun;8(6):1495-500. Oncogene. 1993. PMID: 8502475
-
Wild-type p53 and a p53 temperature-sensitive mutant suppress human soft tissue sarcoma by enhancing cell cycle control.Clin Cancer Res. 1998 Aug;4(8):1985-94. Clin Cancer Res. 1998. PMID: 9717829
-
Stable nontumorigenic phenotype of somatic cell hybrids between malignant Burkitt's lymphoma cells and autologous EBV-immortalized B cells despite induction of chromosomal breakage and loss.Cancer Res. 1998 Nov 1;58(21):4930-9. Cancer Res. 1998. PMID: 9810002
-
[P53 genes and malignant hematologic diseases].Bull Cancer. 1993 Aug;80(8):697-703. Bull Cancer. 1993. PMID: 8204951 Review. French.
Cited by
-
Histone deacetylase inhibitor potentiates chemotherapy-induced apoptosis through Bim upregulation in Burkitt's lymphoma cells.J Cancer Res Clin Oncol. 2012 Feb;138(2):317-25. doi: 10.1007/s00432-011-1093-y. Epub 2011 Dec 1. J Cancer Res Clin Oncol. 2012. PMID: 22131152
-
Rac1 targeting suppresses p53 deficiency-mediated lymphomagenesis.Blood. 2010 Apr 22;115(16):3320-8. doi: 10.1182/blood-2009-02-202440. Epub 2010 Feb 23. Blood. 2010. PMID: 20179179 Free PMC article.
-
Epstein-Barr virus and Burkitt lymphoma.J Clin Pathol. 2007 Dec;60(12):1397-402. doi: 10.1136/jcp.2007.047977. J Clin Pathol. 2007. PMID: 18042696 Free PMC article. Review.
-
Vasostatin, a calreticulin fragment, inhibits angiogenesis and suppresses tumor growth.J Exp Med. 1998 Dec 21;188(12):2349-56. doi: 10.1084/jem.188.12.2349. J Exp Med. 1998. PMID: 9858521 Free PMC article.
-
Wild-type TP53 defined gamma-secretase inhibitor sensitivity and synergistic activity with doxorubicin in GSCs.Am J Cancer Res. 2019 Aug 1;9(8):1734-1745. eCollection 2019. Am J Cancer Res. 2019. PMID: 31497354 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Research Materials
Miscellaneous